AACR, Author Interviews, Biomarkers, Breast Cancer, Cancer Research / 11.04.2024

MedicalResearch.com Interview with: RJ Tesi M.D. CEO and Founder of INmune Bio MedicalResearch.com: What is the background for this study? What are the main findings?
  • MUC4 expression by high-risk breast cancer (HER2+ or TNBC) is a biomarker that predicts resistance to therapy and an increased risk a metastasis. MUC4 expression can be determined at time of biopsy and therapeutic decisions should be adjusted to optimize the chance of response to first line therapy.
This biomarker is easily determined using immunohistochemistry in the diagnostic breast biopsy tissue similar to testing for HER2 expression. Testing for MUC4 can be easily added to the current panel of routine stains obtained at the time of the diagnostic biopsy. Knowing MUC4 status in women with high-risk breast cancer will improve results.
  • Soluble TNF causes the up regulation of immune checkpoint proteins of cells of the TME. This includes CD47 and SIRPa on tumor based macrophages and CTLA4, PD1, LAG3 and TIGIT on T cells in the TME. INB03 is a pan immune checkpoint modulator. Treatment with INB03 downregulates all immune checkpoint proteins on the cells. Downmodulation of all immune checkpoint proteins improves response to immunotherapy.
Currently, monoclonal antibodies targeting immune checkpoint proteins are a mainstay of cancer therapy and cancer drug development. These strategies target one immune checkpoint protein at a time. To date, combination therapy targeting two immune checkpoint proteins has been tried (e.g.: anti-PD1 and anti-CTLA4 combination therapy) with mixed results. Combination immune checkpoint strategies may increase therapeutic response but increase toxicity. INB03 downregulates all immune checkpoint proteins. This is equivalent to giving a patient a 6 antibody cocktail – something that cannot be done in man. As expected, decreased immune checkpoint expression improves response to therapy by converting immunotherapy resistant tumors to immunotherapy sensitive tumors.
  • In TNBC, MUC4 expression predicts both resistance to anti-PD1 therapy and increased risk of distant metastasis. Treatment with INB03 decreases expression of proteins associated with tumor metastasis, decreases the number of metastasis and improves response to anti-PD1 therapy. Early use of INB03 may prevent distal disease and improve tumor control.
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