Daud et al. – This report describes the first human trial of gene transfer utilizing in vivo DNA electroporation, headed by Dr. Adil Daud, M.D. at University of California, San Francisco. Adil’s Phase I study laid the groundwork for OncoSec’s formation and his expertise has proven integral to the Company’s development. The results indicate this modality to be safe, effective, reproducible, and titratable.
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Kerker et al. – Restifo’s group at the NIH conducted a set of experiments evaluating the immunologic effects of IL-12 on the tumor by engineering tumor-specific CD8+ T-cells to secrete a functional single-chain IL-12. This paper very eloquently demonstrates that IL-12 triggers programmatic changes in myeloid-derived suppressor cells (MDSCs), macrophages, and dendritic cells within the tumor microenvironment, which enables increased antigen processing and presentation without altering T-cell receptor avidity. This is a critical finding because it elucidates a mechanism of action for IL-12 that highlights how it can convert a tumor with minimal T-cell infiltration into a tumor with high infiltration of T-cells via the reprogramming of APC’s.
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Kohrt et al. – Dr. Holbrook Kohrt (the newest member of our SAB) has been an academic leader in advancement of intratumoral immuno-oncology therapies. This paper outlines potential combination strategies with checkpoint inhibitors and intratumoral therapies that make sense based on biologic rationale.
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Spranger et al. – This paper provides an understanding of the Low versus High TIL tumor phenotypes, and discusses why a High TIL phenotype is more likely to respond to checkpoint inhibitor therapies like anti-PD-1 mAb. It also explains the need for the same immune signature discussed in our presentations, which is required for anti-PD-1 response, I.e. IFN-g driven biomarkers like IDO, PD-L1, and other chemokines like CXCL-9 and CXCL-10.
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Marabell et al. – This French group, in collaboration with Dr. Kohrt, produced this seminal paper that lays out a strong rationale for why intratumoral therapies represent a new paradigm in cancer treatment. They propose that companies have fallen into the trap of trying to develop immunotherapeutic agents as “typical anti-cancer drugs”, and administering them systemically. However, the next generation of immune-modulating drugs are designed to target the immune system, rather than the tumor itself. Thus, these therapies should be delivered intratumorally, where they can act on specific immune cells, as opposed to being delivered systemically, which can result in “off-target” toxic effects.
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Pardoll, D. M. – This paper provides an overview of the immunosuppressive mechanisms deployed by tumors as they pertain to checkpoint inhibitor therapies. Importantly, this paper is also where Dr. Pardoll first coins the term, “adaptive resistance”, which describes the ability of cancer cells to adapt their biology to evade destruction.
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