The majority of patients with solid tumors who have been treated with anti-PD-1/PD-L1 therapies do not respond to treatment: this is one of the great challenges in oncology today. OncoSec believes TAVO may address this unmet medical need by increasing the proportion of patients who will respond to anti-PD-1 and other checkpoint therapies.
Anti-PD1/PDL1 mAb Non-Response
~ 60 – 80%
Triple Negative Breast (TNBC)
~ 70% – 82%
Renal Cell Carcinoma (RCC)
Lung Carcinoma (NSCLC)
~ 79 – 83%
Head and Neck (H&N)
1 Patients were preselected by Merck PD-L1 IHC assay 2 11% in PD-L1 (Roche) negative: 43% in PD-L1 + population
HOW IT WORKS
Certain cancers can bypass or hide from the immune system by engaging an immune checkpoint called PD-1, which is a protein found on T-cells. PD-1 represents an “off-switch” which cancers can exploit to escape from T-cells, which are critical to the immune system’s anti-tumor attack. New treatments, called checkpoint inhibitors, block these “off-switches” and help keep T-cells in attack mode to fight cancer cells.
Patients who possess “switched-off” anti-tumor CD8+T-cells in their tumors (i.e. increased tumor-infiltrating lymphocytes, or TILs) are most likely to respond to therapy with anti-PD1 or anti-PD-L1 drugs. However, studies show that these TILs – the target cell for T-cell checkpoint agents – are lacking in the majority of patients. As a result, anti-PD-1 non-responders constitute the majority of patients with solid tumors.
Pre-clinical data indicates that local delivery and expression of TAVO promotes tumor immunogenicity and increases TILs. As a pro-inflammatory cytokine, IL-12 can promote the recruitment of T-cells to the tumor. By driving T-cells or TILs into the tumor microenvironment, TAVO may enhance response to anti-PD-1 and convert anti-PD-1 non-responders to responders.
The following scientific resources provide additional information about immune checkpoint therapies in cancer immunotherapy.
Herbst RS, et. al. “Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients.” Nature. 2014 Nov27;515(7528): 563–567. doi:10.1038/nature14011. >> Read More
Tumeh PC, et. al. “PD-1 blockade induces responses by inhibiting adaptive immune resistance.” Nature. 2014 Nov 27;515(7528):568-71. doi: 10.1038/nature13954. >> Read More
Pardoll DM. “The blockade of immune checkpoints in cancer immunotherapy.” Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239. >> Read More
“Tumor Immunogenicity: The Role of PD-1 and TILs.” Presented by Dr. Robert H. Pierce, MD, Chief Scientific Officer, OncoSec Medical >> See Video