Phase I/II study of adoptive T-cell therapy following in vivo priming with a HER2/neu
 

Phase I/II study of adoptive T-cell therapy following in vivo priming with a HER2/neu vaccine in patients with advanced-stage HER2⁺ breast cancer.



Abstract No:
615
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Author(s): Mary L. Disis, Andrew L Coveler, Doreen Higgins, Leonard A D'Amico, Chihiro Morishima, James Ross Waisman, Jessica Reichow, Jennifer Childs, Yushe Dang, Lupe G. Salazar, Edmond Marzbani; University of Washington, Seattle, WA; City of Hope, Duarte, CA
Abstract Disclosures

Abstract:

Background: We have reported that infusion of ex vivo expanded T cells derived from previously HER2-vaccine-primed PBMC is safe and able to mediate an anti-tumor response in patients with HER2⁺ breast cancer (Disis 2013). In this study, we evaluated the safety and clinical efficacy of infusion of HER2 specific T cells after rapid HER2 vaccinations in patients with advanced stage HER2⁺ breast cancer. Methods: 19patients were vaccinated three times weekly with a HER2 peptide based vaccine. HER2 specific T-cells were expanded 2 weeks after 3^rd vaccine. The patients received 2-3 escalating doses of T-cells given at 7-10 day intervals. Cyclophosphamide was administrated before the first dose of T- cells. One patient underwent indium-111 labeling of T-cells for SPECT/CT scanning. Results: All patients received at least two doses of HER2 specific expanded T-cells. The infused T-cell products were >98% of CD3⁺ with an average of 43% CD4⁺ and 54% CD8+ T-cells. The total number of T-cells infused was 0.3x10⁹ – 57.1x10⁹ (median 17.5x10⁹). Subjects tolerated the infusions well with 95% of adverse events of grade 1 or 2. There were no complete or partial responses. 59% had stable disease (SD) 1-3 months after infusion and 41% of the patients demonstrated progressive disease (PD). The frequencies of HER2 specific T-cells in the infused products were significantly higher in patients with SD than that in PD (p=0.039). The percentage of CD4⁺ cells in products was positively correlated with HER2 specific T-cells (p=0.017). HER2 immunity was generated in vivo and augmented in magnitude after infusion and was maintained 3-9 months post infusion in the majority of patients. SPECT/CT of In-111 labeled T-cells demonstrated cell trafficking to all sites of metastatic disease. Conclusions: Adoptive transfer of HER2 specific T-cells generated from PBMC after rapid immunization is feasible and safe. Clinical outcome is associated with the frequency of HER2 specific CD4 T-cells present in the infusion product. Clinical trial information: NCT00791037.