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Journal of Clinical Investigation
Combination therapy with a monocloncal antibody and a vaccine leads to tumor rejection
Effector T cells (Teff cells) are involved in activating and directing other immune cells, while regulatory T cells (Tregs) act to curb the over-aggressive responses of the T cell population. Researchers continue to work on devising ways to mobilize anti-tumor Teff cells in order to better shape the immune response to tumors. Previously, James Allison and colleagues from Memorial Sloan-Kettering Cancer Center, New York, demonstrated that an anti–CTLA4 monocloncal antibody used in combination with a vaccine expressing GM-CSF (Gvax) was able to eradicate skin and breast cancer in mice. In a new study appearing online on June 15 in advance of print publication in the July issue of the Journal of Clinical Investigation, this same research group investigated the effects of CTLA4 blockade on the balance between Teff cells and Tregs during tumor rejection.
The authors show that when cancer develops in mouse skin cells, Tregs accumulate in tumors, yet CD8+ Teff cells are underrepresented. They go on to demonstrate that blockade of CTLA4 lifts the inhibition of T cell proliferation and allows both Tregs and Teff cells to proliferate in response to exposure to self-antigen. Interestingly, combination of CLTA4 blockade with Gvax selectively primes the anti-tumor Teff cells for action. This led to greater infiltration of Teff cells into the tumor, and eventually to tumor rejection. Importantly, the authors report that chronic exposure to anti- CLTA4 or to the Gvax/anti-CTLA4 combination therapy does not deplete the number of Tregs, nor their regulatory activity, which suggests that upon completion of this therapy these cells would still be able to control possible adverse immune responses.
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