INmune Bio Inc. Presents Data on INB03’s Role as an Immune Check Point Modulator in the Treatment of High-Risk Breast Cancer at AACR 2024 - Seite 2

A second poster, titled, “MUC4 is a biomarker of metastasis in TNBC and its downregulation by blocking soluble TNF prevents metastasis in combination with immunotherapy,” studies the importance of MUC4 expression in TNBC survival.  Approximately half of women with TNBC express MUC4.  Overall survival of women with MUC4 expressing TNBC is dramatically worse (p<0.005) with almost a 5-fold increased risk of death (p<0.018). MUC4 expression in the tumor negatively correlated with fewer Tumor Infiltrating Lymphocytes (TILs, p<0.003), PD-L1 (p<0.001) and Ki67 (p<0.036) expression.   In human TNBC cell lines, INB03 decreased the expression mesenchymal markers of invasive capacity, MUC4, SNAIL and Vimectin, and decreased activity in an invasion assay (p<0.01). 

In a murine LMM3 model, treatment with the combination of INB03 and anti-PD1 checkpoint antibodies dramatically decreased lung metastasis with no animals receiving combination therapy having >3 lesions compared to 40% of control animals (p<0.05).  The authors concluded: i) MUC4 expression is an independent biomarker of poor overall survival and is associated with an increased risk of metastasis in TNBC patients; ii) MUC4 is inversely correlated with TILs, and is associated with tumors with low proliferative rate (Ki67<30%) and negative PD-L1: it would be useful to identify tumors resistant to chemotherapy and immunotherapy; iii) TNF blockade decreases MUC4 expression, mesenchymal markers and reduces invasive capacity in TNBC cell lines;  iv) soluble TNF blockade in combination with anti PD-1 antibody prevents the establishment of lung metastases in a preclinical model of TNBC.  They further propose soluble TNF as a new target for the treatment of TNBC, and MUC4 as a predictive marker to guide a combined treatment with selective sTNF neutralization with immunotherapy. The poster can be found on the Company’s web site.

Dr. Schillaci, senior author of the study, proposes INB03 is a new class of immunotherapy called a pan immune checkpoint modulator in MUC4 expressing breast cancer.  INB03 isn't a selective immune checkpoint inhibitor targeting a specific immune checkpoint protein; rather, it downregulates all immune checkpoint proteins present on both T cells and macrophages. “Soluble TNF, secreted by cancer cells, shields tumors from immune attacks by altering the tumor microenvironment, rendering the patient's immune response ineffective and fostering resistance to immunotherapy. Through extensive research, we have unraveled the mechanisms underlying the tumor protecting role of soluble TNF which causes tumors to proliferate. Translating these findings into targeted strategies for high-risk breast cancer, we can devise a precision medicine approach to counteract soluble TNF's effects, reversing therapy resistance, preventing  metastasis, and empowering the immune system to combat tumors effectively,” said Dr. Schillaci