Genspera's G202: 12ADT toxin unwrapped by enzymes, "effective monotherapy"
G202: 12 year old project originally targeted plant toxin thapsigargan to prostate specific membrane antigen (PSMA)..until it was discovered that other cancers had similar targets. Inactivated toxin travels through blood and is "unwrapped" by target enzymes on cancer cells. Attacks vasculature of tumor like Avastin. But unlike Avastin (which inhibits growth only while being used), G202 collapes tumor vasculature. Claims to be a stand-alone therapy capable of killing all cancer cells with target enzyme(s), including cancer stem cells. Works before drug resistance mechanisms can react. Can be reused.
Expensive preclinical studies included rats and monkeys with multiple rounds of dosing, making for higher quality data, better toxicology study and quicker trial approval. Side effects are said to be rapidly reversible.
"It looks like what we've seen in animals will be replicated in humans—that's what we expect to see," Dionne said.
Not to get too overly optimistic: the drug is in the earliest phase of FDA clinical trials. So far, researchers are excited and hopeful because they've cranked up the dosage more than they ever thought possible, and still have not seen side-effects in patients. Twenty-six patients with various types of late-stage "solid tumor" cancer have participated in the trial and researchers will soon add 18 more. After that they hope to move on to the second phase of trials (FDA clinical trials usually include three phases: the first for safety, the second for safety and efficacy, and the final one to confirm safety and efficacy.)
Posted :
Fri, 11 Sep 2009 12:06:00 GMT
SAN ANTONIO - (Business Wire) GenSpera, Inc.
announced today that the Food and Drug Administration (FDA) has approved its Investigational New Drug (IND) application to begin a Phase I study with its target activated pro-drug, G-202, for the treatment of cancer. GenSpera’s Phase I clinical study is anticipated to begin in the fourth quarter of 2009 at two major cancer centers: the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, in Baltimore, MD, and the University of Wisconsin Carbone Cancer Center, in Madison, WI. The study is designed to enroll patients with cancers that have progressed after treatment with other anti-cancer agents. The primary endpoints of the open-label, dose-escalation study will be to determine the safety, tolerability and pharmacokinetics of the drug, although the design allows the collection of efficacy data as well. “The acceptance of our IND by the FDA constitutes a defining milestone in the development of an entirely new class of anti-cancer agent that is expected to have broad utility across many tumor types,” commented Dr. Craig Dionne, GenSpera CEO. “We are also pleased that this event underscores the company’s drug development capabilities and commitment to timely achievement of important corporate milestones.” G-202 is a pro-drug that is selectively activated within tumors by an enzyme present on the tumor blood vessels. In preclinical testing, G-202 was shown to ablate tumors in animal models of breast cancer, prostate cancer and kidney cancer. GenSpera, Inc. owns and controls all rights to G-202 and anticipates a strategic partnership to maximize the value of the drug as it progresses through future clinical trials. About GenSpera
GenSpera, Inc. is a development stage oncology company focused on therapeutics which deliver a potent, unique and patented drug directly to tumors. GenSpera’s technology platform combines a potent cytotoxin (12ADT) with a pro-drug delivery system that activates the drug only within the tumor. Unlike standard cancer drugs, plant-derived 12ADT kills cells independent of their division rate, thus making it effective at killing all fast- and slow- growing cancers and cancer stem cells. GenSpera’s pro-drug platform is the subject of six issued patents with six additional patents pending.
GenSpera plans to initiate a Phase I cancer trial with its lead drug, G-202, in the fourth quarter of 2009. G-202 targets the established blood vessels that nourish solid tumors, thus destroying the tumor’s blood supply. This is a dramatic improvement upon anti-angiogenic drugs that primarily only stop the growth of new blood vessels. Upon completion of its Phase I trial, GenSpera expects to initiate multiple Phase II trials for G-202 in several different cancer types. The company’s second drug, G-115, will directly target prostate cancer.
For more information, please visit the Company’s website: www.genspera.com.
GenSpera, Inc. (OTCBB: GNSZ) announced today that the Institutional Review Board (IRB) at the University of Wisconsin, in Madison, WI, has approved a Phase I study of its target activated pro-drug, G-202, for the treatment of cancer. The FDA (US Food and Drug Administration) approved the study in September. GenSpera expects to enroll the first study patient early in the first quarter of 2010.
The G-202 Phase I study is designed to enroll up to thirty patients with cancers that have progressed after treatment with other anti-cancer agents. The primary endpoints of the open-label, dose-escalation study are to determine the safety, tolerability and pharmacokinetics of the drug, although the design allows the collection of efficacy data as well. Patients will also accrue at a second major cancer center, subject to its IRB approving the study.
“This IRB approval is another important milestone for GenSpera as we now move into full-fledged clinical stage operations with our lead drug, G-202,” said Dr. Craig Dionne, CEO, GenSpera, Inc. “We look forward to working closely with our Phase I sites, which are internationally recognized leaders in clinical cancer research.”
“We are excited that this clinical trial has been activated at the University of Wisconsin Carbone Cancer Center,” said Dr. George Wilding, Director of the Carbone Cancer Center and the Principal Investigator (PI) for the study. “G-202 is a novel approach to the treatment of cancer and we hope that it has a significant effect for those patients whose lives are affected by this disease.”
Patients interested in enrolling in the G-202 trial may contact the University of Wisconsin Carbone Cancer Center Connect line at 800-622-8922.
SOURCE GenSpera, Inc.
Anticancer Agents Med Chem. 2009 Mar;9(3):276-94. A Trojan horse in drug development: targeting of thapsigargins towards prostate cancer cells.
Christensen SB, Skytte DM, Denmeade SR, Dionne C, Møller JV, Nissen P, Isaacs JT.
Department of Medicinal Chemistry, University of Copenhagen, Denmark. sbc@farma.ku.dk
Available chemotherapeutics take advantage of the fast proliferation of cancer cells. Consequently slow growth makes androgen refractory prostate cancer resistant towards available drugs. No treatment is available at the present, when the cancer has developed metastases outside the prostate (T4 stage). Cytotoxins killing cells irrespective of the phase of the cell cycle will be able to kill slowly proliferating prostate cancer cells. Lack of selectivity, however, prevents their use as systemic drugs. Prostate cancer cells secrete characteristic proteolytic enzymes, e.g. PSA and hK2, with unusual substrate specificity. Conjugation ofcytotoxins with peptides, which are selective substrates for PSA or hK2, will afford prodrugs, from which the active drug only will be released in close vicinity of the cancer cells. Based on this strategy prodrugs targeted at prostate cancer cells have been constructed and evaluated as potential drugs for prostate cancer. The potency of the thapsigargins as apoptotic agents make these naturally occurring sesquiterpene lactones attractive lead compounds. Intensive studies on structure-activity relationships and chemistry of the thapsigargins have enabled construction of potent derivatives enabling conjugation with peptides. Studies on the mechanism of action of the thapsigargins have revealed that the cytoxicity is based on their ability to inhibit the intracellular sarco-/endoplasmtic calcium pump.
PMID: 19275521 [PubMed - indexed for MEDLINE]
The Kallikreins target the toxin to various cancers:
Cancer Lett. 2005 Jun 16;224(1):1-22. Human tissue kallikrein gene family: applications in cancer.
Obiezu CV, Diamandis EP.
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ont., Canada M5G 1X5.
Human tissue kallikrein genes, located on the long arm of chromosome 19, are a subgroup of the serine protease family of proteolytic enzymes. Initially thought to consist of three members, the human kallikrein locus has now been extended and includes 15 tandemly located genes. These genes, and their protein products, share a high degree of homology and are expressed in a wide array of tissues, mainly those that are under steroid hormone control. PSA (hK3) is one of the human kallikreins, and is the most useful tumor marker for prostate cancer screening, diagnosis, prognosis and monitoring. hK2, another prostate-specific kallikrein, has also been proposed as a complementary prostate cancer biomarker. In the past 5 years, the newly discovered kallikreins (KLK4-KLK15) have been associated with several types of cancer. For example, hK4, hK5, hK6, hK7, hK8, hK10, hK11, hK13 and hK14 are emerging biomarkers for ovarian, breast, prostate and testicular cancer. New evidence raises the possibility that some kallikreins are directly involved with cancer progression. We here review the evidence linking kallikreins and cancer and their applicability as novel biomarkers for cancer diagnosis and management.
Expression of Human Prostate-specific Glandular Kallikrein Protein (hK2) in the Breast Cancer Cell Line T47-D1
Ming-Li Hsieh, M. Cristine Charlesworth, Marcia Goodmanson, Shaobo Zhang, Thomas Seay, George G. Klee, Donald J. Tindall and Charles Y. F. Young2
Departments of Urology [M-L. H., S. Z., T. S., D. J. T., C. Y. F. Y.], Biochemistry and Molecular Biology [M. C. C., D. J. T., C. Y. F. Y.], and Laboratory Medicine [M. G., G. G. K.], Mayo Graduate Schools, Mayo Clinic/Foundation, Rochester, Minnesota 55905
Human glandular kallikrein (hK2) protein, like prostate-specificantigen (PSA), is produced mainly in prostatic epithelium. Itmay be useful as a new diagnostic indicator for prostate cancer.Recently, a number of hK2-specific monoclonal antibodies havebeen developed that enable us to detect hK2 protein in humanprostate tissue, seminal fluid, and sera. Whether hK2 can beexpressed, like PSA, in nonprostatic cells is not known. Inthis study, we have characterized the presence of hK2 in anandrogen-responsive breast cancer cell line T47-D at both theprotein and mRNA levels with an immunoassay, Western blot analysis,Northern blot analysis, and the reverse transcription-PCR.
Using a sensitive immunoassay with monoclonal antibodies tohK2, we found that T47-D cells could be induced with androgens,mineralocorticoids, glucocorticoids, and progestins to producesignificantly more hK2 than PSA. Estrogens failed to mimic theeffect of the other steroids, blocking instead the stimulatoryeffect of androgens. Androgen induction of hK2 in T47-D cellswas dose dependent. More interestingly, we found that the hK2in androgen-induced T47-D cell spent media appears to be thepro-form of hK2 rather than mature hK2.
Our study demonstrates that hK2, a serine protease thought tobe found only in prostate-related tissues and fluids, is alsoproduced in a breast cancer cell line T47-D after steroid stimulation.This finding suggests that hK2 may have a potential role inbreast cancer as well as prostatic cancer and will be the impetusfor further studies of hK2 distribution and function.
J Cell Sci. 2009 Dec 15;122(Pt 24):4481-91. Epub 2009 Nov 17. Inhibition of the ER Ca2+ pump forces multidrug-resistant cells deficient in Bak and Bax into necrosis.
Janssen K, Horn S, Niemann MT, Daniel PT, Schulze-Osthoff K, Fischer U.
Interfaculty Institute for Biochemistry, University of Tübingen, Tübingen, Germany. Tumor cells deficient in the proapoptotic proteins Bak and Bax are resistant to chemotherapeutic drugs. Here, we demonstrate that murine embryonic fibroblasts deficient for both Bak and Bax are, however, efficiently killed by thapsigargin, a specific inhibitor of ER Ca(2+) pumps that induces ER stress by depleting ER Ca(2+) stores. In the presence of Bak and Bax, thapsigargin eliminates cells by release of mitochondrial cytochrome c and subsequent caspase activation, which leads to the proteolytic inactivation of the molecular necrosis switch PARP-1 and results in apoptosis. By contrast, in the absence of Bak and Bax, a failure to activate caspases results in PARP-1-mediated ATP depletion. The subsequent necrosis is not prevented by autophagy as an alternative energy source. Moreover, in cells deficient for both Bak and Bax, thapsigargin induces permanent mitochondrial damage by Ca(2+) overload, permeability transition and membrane rupture. Thus, even though deficiency in Bak and Bax protects these cells against apoptosis, it does not compromise necrosis induced by SERCA inhibitors. Importantly, thapsigargin induces caspase-independent cell death also in colon and prostate carcinoma cells deficient in Bak and Bax expression. Therefore, targeted application of ER stressors such as thapsigargin might be a promising approach for the treatment of Bak- and Bax-deficient, drug-resistant tumors.
PMID: 19920074 [PubMed - in process]
Combination Approach may Detect or Treat Prostate Cancer
Prostate cancer is one of the areas in oncology that has extensive research ongoing to identify a precise diagnostic and therapeutic. Prostate Specific Antigen (PSA) testing is widely used to detect cancerous patients, which comes along with certain limitations such as false positives and low sensitivity. Majority of the patients adopt either a focused treatment or the watchful waiting approach. Dual imaging and novel therapy for prostate cancer, are the need of the hour. Researchers have reported a manner to put together chemotherapy and imaging to treat prostate cancer.
Associate professor of oncology, Samuel R. Denmeade tells Technical Insights, "The Smart Bomb is being developed in our lab in collaboration with Dr. John Isaacs at Johns Hopkins. This technology is an extension of our long-term work on development of prostate cancer protease activated drugs. We have focused on drugs activated by PSA and PSMA. The radiolabeled imaging idea grew out of our observations in animals that high levels of drug built up over time."
The team has generated a prodrug consisting of a peptide that is recognized as a substrate for prostate cancer protease PSMA, which is relatively specific for prostate cancer. This peptide is linked to an analog of the potent cytotoxic natural product thapsigargin. The peptide and thapsigargin are connected by a linker containing a radioactive iodine label. This label can be either hot enough for imaging or even hotter for therapy. The prodrug circulates in the blood and, upon encountering PSMA producing cells, the labeled thapsigargin molecule is liberated and sticks in the tumor tissue. The labeled drug builds up over time and can then be imaged. It could also deliver therapeutic doses of radiation given a more radioactive label.
To date, the team has identified PSMA specific peptides, and a thapsigargin analog that can be labeled. They have made the "smart bomb" labeled with 125-I and have started to evaluate its potential as an imaging agent in animals.
This project was initially funded by the Prostate Cancer Foundation, followed by the Dept of Defense (DoD) Prostate Cancer Research Program. The current funding is also from DoD.
The technology is currently covered by 7 issued patents. Moreover, it has been licensed to GenSpera, Inc. a start-up company based in San Antonio Texas. GenSpera is in clinical development of a therapeutic prodrug that lacks the radiolabel but hopes to be in clinical trial by fall-winter of 2009. Details:
Samuel R. Denmeade MD,
Associate Professor of Oncology
Chemical Therapeutics Program
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Prostate-specific membrane antigen (PSMA) is a cell surface protein that is expressed at high levels in the vasculature of prostate cancer and many other solid tumor types at all stages of the disease, making it a key target for therapy. PCRP investigators are taking advantage of the biological activities and unique patterns of expression of PSMA and other similar molecules by developing varied strategies to deliver targeted therapy. For example, harnessing molecule and tissue specificity is a crucial part of the highly potent therapy being developed by Johns Hopkins University (JHU) researcher Dr. Samuel Denmeade (pictured left), a recipient of FY01 and FY06 Idea Development Awards. Dr. Denmeade has taken advantage of the toxic properties of thapsigargin (TG), a plant toxin that kills all cells independent of proliferation rate and tissue type. TG does this by blocking the sarco(endo) plasmic reticulum Ca++ ATPase (SERCA) pump from transporting calcium across the sarco(endo)plasmic reticulum membrane. Given its universal effect, the toxin must first be rendered safe for healthy tissues. To accomplish this task, Dr. Denmeade synthesized inactive analogs (prodrugs) of TG and attached them to a specific peptide carrier, chosen because it also serves as a substrate for PSMA. Only in the presence of PSMA, the cytotoxin was released from the prodrug into the local environment.
The prodrugs were stable and exhibited 15- to 57-fold higher toxicity to prostate cancer cells than normal cells. One lead prodrug demonstrated complete and sustained inhibition of prostate cancer tumor growth with minimal toxicity to healthy tissue (Figure 1).
Titles
Associate Professor of Oncology Schools/Degrees
M.D., Columbia College of Physicians and Surgeons, Columbia University, New York, NY
Training
Intern, University of Chicago Hospitals and Clinics, Chicago, IL
Residency, University of Chicago Hospitals and Clinics, Chicago, IL
Clinical Fellow in Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD
Certifications
Internal Medicine, Medical Oncology
Clinical Interests
Prostate Cancer, Targeted Drug Development, Bladder Cancer, and Renal Cancer
Research Summary
Cancer produces its lethal effects because it continues to grow. Growth occurs because the number of cancer cells producing daughter cells (i.e., division) is greater than the number of cells dying. Within prostate cancer patients, however, the number of cancer cells dividing is remarkably low. The reason prostate cancers continue to grow is that the number of cancer cells dying is even lower. Despite the small difference in the rate of division vs. death of prostate cancer cells, this imbalance results in the death of 31,000 men in the United States per year due to the continuous growth of prostate cancer cells spreading throughout the body. Chemotherapy usually kills cells only when they are dividing. In men with widespread prostate cancer, the rate of division is so low that these cells are only minimally killed by chemotherapy. In contrast to these ineffective agents, a natural product of a plant called thapsigargin (TG) caused the death of prostate cancer cells without requiring cell division. TG's potent ability to kill nondividing prostate cancer cells is not unique, however. TG also can kill normal non-cancer cells. To target TG's killing ability to prostate cancer cells only, Dr. Denmeade's lab is chemically making changes to the TG molecule to produce inactive drugs (prodrugs), which are themselves unable to kill normal cells throughout the body, or prostate cancer cells. These prodrugs are designed so that they can be converted to killing agents only by prostate cancer cells at sites of prostate cancer throughout the body. This is based on the ability of prostate cancers to produce a class of protein called proteases that are able to cut other proteins into smaller pieces. Since these proteases are produced at high levels only by prostate cancer cells and not by normal cells, this strategy represents a new way to target the killing ability of a very potent new drug, TG, to prostate cancer cells while avoiding side effects to the rest of the body.
Cancer Biol Ther. 2005 Jan;4(1):14-22. Epub 2005 Jan 23. The SERCA pump as a therapeutic target: making a "smart bomb" for prostate cancer.
Denmeade SR, Isaacs JT.
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. denmesa@jhmi.edu
Prostate cancer is uniformly fatal once it has spread outside of the prostate gland. Prostate cancers have a remarkably low proliferative rate, which may in part explain their relative unresponsiveness to conventional antiproliferative chemotherapy. New therapies for prostate cancer that activate proliferation independent cell death are therefore needed. The endoplasmic reticulum (ER) has emerged as an organelle that plays a major role in cell signaling pathways, cellular response to stress and cellular activation of apoptosis. In this review, the SERCA pump is identified as an ER protein whose normal function is required by all cells and represents a potential therapeutic target for cancer therapy. Sustained SERCA inhibition by agents such as thapsigargin results in activation of ER-stress response and simultaneous activation of apoptotic pathways within the ER and the mitochondria. Due to the SERCA pump's critical role in normal cellular metabolism, agents like thapsigargin directed toward inhibiting SERCA function would likely produce significant toxicity to normal cells and, therefore, must be selectively targeted to cancer sites. The cytotoxicity of thapsigargin can be attenuated, however by coupling to a targeting peptide to produce an inactive prodrug that is only activated by prostate cancer specific proteases such as the serine protease prostate-specific antigen (PSA). PSA-activated thapsigargin prodrugs have been characterized that are selectively toxic to PSA-producing prostate cancer cells in vitro and in vivo. These prodrugs are currently undergoing preclinical evaluation as potential targeted therapy for prostate cancer.
PMID: 15662118 [PubMed - indexed for MEDLINE]
Arch Biochem Biophys. 2007 Aug 1;464(1):19-27. Epub 2007 Apr 16. Mechanisms of resistance and adaptation to thapsigargin in androgen-independent prostate cancer PC3 and DU145 cells.
Lee DI, Sumbilla C, Lee M, Natesavelalar C, Klein MG, Ross DD, Inesi G, Hussain A.
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Cells with increasing resistance to the sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA) inhibitor thapsigargin (TG), ranging from 60-fold (PC3/TG(10) cells) to 1350-fold (PC3/TG(2000) cells), were derived from PC3 cells. SERCA2 is overexpressed in all PC3/TG cells but retains sensitivity to TG. siRNA-mediated downregulation of SERCA completely or partially reverses TG resistance in PC3/TG(10) or PC3/TG(2000) cells, respectively; thus SERCA overexpression mediates resistance in PC3/TG(10) cells but is not the only resistance mechanism in PC3/TG(2000) cells. By contrast, SERCA is not overexpressed in TG-resistant DU145/TG cells derived from DU145 cells. DU145/TG cells retain resistance while in PC3/TG cells resistance decreases upon removal of TG selection. The transport proteins PGP/BCRP/MRP1 and anti-apoptotic proteins Bcl2/Bcl(XL) are not involved in mediating resistance in either cell line. PARP and caspase 3 cleavage in response to other drugs demonstrate that the apoptotic pathways tested remain intact in these cells. Further, no cross-resistance occurs to other drugs. Thus, novel TG-specific resistance mechanisms are recruited by these cancer cells.
PMID: 17475205 [PubMed - indexed for MEDLINE]
en Physiol Biophys. 2008 Sep;27(3):211-21.Overexpression of P-glycoprotein in L1210/VCR cells is associated with changes in several endoplasmic reticulum proteins that may be partially responsible for the lack of thapsigargin sensitivity.
Seres M, Poláková E, Krizanová O, Hudecová S, Klymenko SV, Breier A, Sulová Z.
Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Vlárska 5, Bratislava, Slovakia.
L1210/VCR cells, which express an abundant amount of P-glycoprotein (P-gp), were found to be resistant to thapsigargin--an inhibitor of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA). In the current paper, we have studied the possible differences among L1210 and L1210/VCR cells in expression of endoplasmic reticulum proteins involved in the regulation of calcium homeostasis and calcium-dependent processes. Amounts of mRNA encoding both calcium release channels (ryanodine receptor channels--RyR and IP3-receptor channels--IP3R) were found to be at similar levels in sensitive and resistant cells. However, mRNAs encoding IP3R1 or 2 were decreased in resistant cells cultivated in the presence of VCR (1.08 micromol/l), while mRNA encoding RyR remained unchanged. The amount of mRNA for SERCA2 was decreased in resistant cells when compared with sensitive cells. This decrease was more pronounced when resistant cells were cultivated in the presence of vincristine (VCR). Calnexin was found to be less expressed at the protein level in resistant as in sensitive cells. The level of mRNA encoding calnexin was decreased only when resistant cells were cultivated in the presence of VCR. Calnexin was found to be associated with immature P-gp in resistant cells. Thus, differences exist between sensitive and resistant cells in the expression of endoplasmic reticulum proteins involved in the control of intracellular calcium homeostasis or calcium-dependent processes. These changes may be at least partially responsible for the lack of sensitivity of resistant cells to thapsigargin.
PMID: 18981537 [PubMed - indexed for MEDLINE]
Trends Endocrinol Metab. 1998 Oct 1;9(8):310-6. Prostate-specific Antigen: Its Usefulness in Clinical Medicine.
Diamandis EP.
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada.
Prostate-specific antigen (PSA) was discovered about 20 years ago and over the last decade it has become the premier tumor marker for diagnosis, monitoring and prognosis of prostatic carcinoma. PSA is now considered to be the best tumor marker available in clinical medicine. It is the only tumor marker that has been approved by the Food and Drug Administration of the USA for mass screening: for the purpose of diagnosing early prostatic carcinoma. Among the newest developments in the field are the discovery of the molecular forms of PSA in serum, the development of ultrasensitive assays that allow better monitoring of patients after radical prostatectomy, and the discovery of non-prostatic PSA. Indeed, there are indications that PSA might be useful for the diagnosis and prognosis of breast cancer. The genomic structure of PSA and other human kallikrein genes and the regulation of their expression has recently been elucidated. Currently, the PSA promoter and enhancer are being investigated in connection with gene therapy in prostatic tissue. Efforts are now underway to supplement the clinical value of PSA measurements with additional prostatic markers, including human kallikrein 2 (hK2) and prostate-specific membrane antigen (PSMA).
Genspera's G202: 12ADT toxin unwrapped by enzymes, "effective monotherapy"
Samuel Denmeade, M.D.
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