Purpose: The heat shock proteins (HSPs) of Mycobacterium have been identified as immunogenic antigens with chaperone functions. This study evaluated a method to enhance host immune responses against cancer cells by utilizing commercial antibodies conjugated with HSP70 derived from Mycobacterium avium subsp. paratuberculosis . Methods: Recombinant HSP70, in conjugation with the monoclonal antibodies trastuzumab and bevacizumab, was employed for both in vivo and in vitro treatment of tumor cells. The cytotoxicity of the antibody-HSP70 complex was assessed on the MCF-7, LS174T, and HEK293T cell lines, after characterization of the cells for expression of the targets. The stimulation of complement activation pathways was examined using a complement fixation assay. The in vivo effects of the HSP70- antibodies were evaluated against xenograft LS174T and MCF-7 tumors in mice. The tumor tissues were evaluated through histopathological analysis. Results: The cytotoxic effect of the antibody-HSP70 complex was significantly greater than that of other treatments against the MCF-7 and LS174T cell lines; this effect was confirmed in the presence of human plasma and leukocyte samples. Additionally, activation of the classical complement pathway has been demonstrated using HSP70 antibodies. Treatment of xenograft tumors with the antibody-HSP70 complex significantly reduced both tumor weight and growth rate, as well as decreased the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1). Histopathological analysis, along with the observed therapeutic efficacy, confirmed the safety of this approach. Conclusion: Overall, stimulating the immune system against cancer cells by targeting innate immune responses could enhance the effectiveness of targeted therapies. Keywords: heat shock protein 70, Mycobacterium avium subspecies paratuberculosis , cancer, antibody
Khosravi et al. (Sun,) studied this question.