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Replies to post #733636 on NorthWest Biotherapeutics Inc (NWBO)
Hyperactivating Stimuli Protect against Established Tumors That Are Resistant to Anti-PD1 Therapy
To determine if hyperactivating stimuli could be harnessed as a cancer immunotherapy, we examined anti-tumor responses in mice that harbored a growing tumor prior to any treatment. For these studies, rather than using parental in vitro cultured tumor cells as an antigen source, ex vivo WTLs were generated using syngeneic tumors from unimmunized mice, in which 10-mm harvested tumors were dissociated and then depleted of CD45+ cells. Mice were inoculated s.c. with tumor cells on the left upper back. When tumors reached a size of 3–4 mm, tumor-bearing mice were left untreated (unimmunized) or received an injection on the right flank with ex vivo WTLs and LPS plus PGPC.
Interestingly, hyperactivation-based therapeutic injections induced durable tumor eradication in a range of tumors, such as B16OVA and B16F10 melanoma models, in MC38OVA and CT26 colon cancer tumor models and in Lewis Lung Carcinoma model (LLC1) (Figures 6A–6E and S6A). The efficacy of the immunotherapy was dependent on IL-1ß in all the tested models, since the neutralization of IL-1ß abolished protection conferred by hyperactivating stimuli plus ex vivo WTLs (Figures 6A–6E and S6A).
In addition, CD8+ T cells were crucial for protection against immunogenic tumor models such as B16OVA or MC38OVA tumors, whereas CD4+ and CD8+ T cells were both required for protection against less immunogenic tumors such as CT26, B16F10, and LLC1 (Figures 6A–6E and S6A) (Mosely et al., 2017).
Interestingly, hyperactivation-based immunotherapy was as efficient as anti-PD-1 therapy in the immunogenic B16OVA model, but more efficient in tumor models that are insensitive to anti-PD-1 treatment such as CT26, B16F10, and LLC1 (Figures 6A–6E and S6A).
