Avid Bioservices Inc (CDMO)

[cjgaddy]

PW, I’ve learned a lot about ACT. I have no doubt that the Wolchok Lab is saying in #1651 that the effectiveness either type (the latest of Adoptive TCell Transfer (ACT), be it TCRs or CAR T (ie, the newer gene-modified T cells approaches), is improved by combining with Bavi, and makes for a “highly desirable strategy.”

ABSTRACT (AACR'17 4-3-17 #1651):
“PS Targeting+Adoptive TCell Transfer (ACT) Eliminates Adv. Tumors w/o Off-Target Toxicities, Melanoma”
A viable strategy to treat advanced cancers includes transferring of tumor-specific T cells. T cells that recognize tumor antigens can be expanded and reinvigorated ex-vivo. Furthermore, autologous T cells can be genetically modified to express anti-tumor T cell receptors [TCRs] or chimeric antigen receptors [CARs]. Although the potency and specificity of tumor-specific T cells can be manipulated ex-vivo, once re-infused into patients, the T cells are subjected to immunosuppressive mechanisms established by the tumor. An important immune checkpoint regulator within tumors is phosphatidylserine (PS). Innate immune cells exposed to PS secrete suppressive cytokines and chemokines that can significantly impair the function and activation of anti-tumor T cells. Therefore, monoclonal antibodies that block PS activity can increase the anti-tumor potency of transferred T cells to treat aggressive cancers. Here we show that a PS targeting monoclonal antibody in combination with CD4+ T cells that recognize the melanoma antigen Trp1 can regress very advanced melanomas in all treated mice. Combination of anti-Trp1 CD4+ T cells with other immunomodulatory modalities such as anti-OX40 antibodies, can achieve equivalent treatment rates but these are typically accompanied by severe immune related adverse events. In contrast, in this setting, PS blockade did not show any off-target toxicities. Flow cytometry analysis revealed lower levels of CD206 expression concomitant with higher activation markers in macrophages and neutrophils in tumors from anti-PS treated mice. These results suggest that diminishing suppressive mechanisms locally in adoptive transfer protocols is a highly desirable strategy that can eliminate tumors while minimizing related adverse events.
MORE: http://tinyurl.com/l69gbyf