Avid Bioservices Inc (CDMO)

[JamesGMS]

From the Hawkfan post:

Dr. Lias stated that they have numerous discussions regarding car-t, but there was no interest. In some other discussions, they found our technology interesting, but then said "prove it in a trial”.

In light of the following one has to wonder why NO ONE is interested in "proving it in a trial" - as enhanced SAFETY would provide a huge advantage to any of the current purveyors of the Car-T technology. And particularly as Jedd Wolchok and MSK are so intimately involved with Car-T and now may have a HUMAN clinical trial designed and READY TO GO - it boggles the mind that not even one of the major players such as Gilead, Novartis, Celgene, etc. would not want to throw a few dollars towards the possibility of rapidly becoming "Best in Class" in this arena.

Hopefully Dr. Wolchok has - or will - be talking with the major Car-T players - and Dr. Lias and the BOD should make sure they do so.

AACR’17 2. 4-3-17/8am #1651 - Session: TUMOR MICROENVIRONMENT & CHECKPOINTS [Joint PPHM & Memorial Sloan Kettering]

“Targeting Phosphatidylserine in Combination with Adoptive T Cell Transfer Eliminates Advanced Tumors without Off-Target Toxicities in a Melanoma Preclinical Model” <=NEW(2nd) MSK STUDY

=> Daniel Hirschhorn-Cymerman 1, Sara Sara Schad 1, Sadna Budhu 1, Zhong Hong 1, Xia Yang 1, Hutchins T. Jeff 2, Bruce D. Freimark 2, Michael J. Gray 2, Jedd Wolchok 1, Taha Merghoub [Memorial Sloan Kettering]

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FROM PPHM’s 4-3-17 PR: http://ir.peregrineinc.com/releasedetail.cfm?ReleaseID=1019762

…”Latest Findings from Ongoing Collaboration with Memorial Sloan Kettering (MSK) Support Potential Applications for Combining CAR T & Anti-PS in Treatment of Solid Tumors”…

For this study, a team of MSK researchers led by cancer immunotherapy thought-leaders, Taha Merghoub, Ph.D. and Jedd D. Wolchok, M.D., Ph.D., evaluated and compared the anti-tumor activity and off-target toxicities of adoptive T cell transfer therapy in combination with either PS-targeting antibodies or anti-OX40 antibodies in mice with advanced melanomas.

Whereas PS-targeting and anti-OX40 demonstrated comparable tumor regression when administered in combination with transferred adoptive T cells, only the PS-targeting combination achieved these results without any off-target toxicities.

By contrast, the anti-OX40 treatment combination triggered off-target inflammatory destruction of healthy tissues. Additional study results demonstrated that the PS-targeting antibodies decreased tumor-induced immunosuppression as evidenced by a decrease in immunosuppressive regulatory T cells (Tregs) and M2 macrophages.

This finding is consistent with Peregrine’s belief that bavituximab may modulate the immunosuppressive tumor microenvironment and enhance the activity of immunotherapy agents.

Taha Merghoub, Ph.D., Co-Dir. of the Ludwig Collaborative Laboratory at MSK:

“While adoptive T cell transfer remains one of the most exciting new approaches to treating cancer, to date the toxicity associated with the treatment has limited its potential. We are encouraged that these study results showed that the combination of anti-PS and adoptive T cell treatment led to enhanced anti-tumor effect without any evidence of additional off-target side effects.

“We believe that these findings may support potential applications for this combination in solid tumors in the future.”

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ABSTRACT #1651:

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.

POSTER #1651 IMAGE: http://www.peregrineinc.com/images/stories/pdfs/aacr2017hirschhorn.pdf

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