Research: Triple-negative breast cancer (TNBC) is phenotypic of the deadliest form of breast tumors lacking expression of the estrogen receptor (ER), the progesterone receptor (PgR), and the human epidermal growth factor receptor 2 (HER2). The persistence of highly tumorigenic epidermal growth factor receptor (EGFR), chondroitin sulfate proteoglycan 4 (CSPG4) and CD44-expressing subpopulations, endowed with the self-renewal capacity, has been associated with therapeutic resistance, hence clinical relapses.

To mitigate these undesired events, targeted immunotherapies using antibody-photoconjugate (APC) or antibody-drug conjugate (ADC), were developed to specifically release cytotoxic payloads within targeted cells overexpressing cognate antigen receptors. Therefore, an 1711(scFv)-SNAP, αCSPG4(scFv)-SNAP and αCD44(scFv)-SNAP-tag antibody fusion proteins were engineered through genetic fusion of the respective single-chain antibody fragment (scFv) to a SNAPf-tag fusion protein, capable of self-conjugating with benzylguanine-modified light-sensitive near-infrared (NIR) phthalocyanine dye IRDye700DX (BG-IR700) or the small molecule toxin auristatin-F (BG- AURIF).Binding of the 1711(scFv)/ αCSPG4(scFv)/ αCD44(scFv)-SNAPf-IR700 photoimmunoconjugates to their respective antigen-positive cells was demonstrated by confocal microscopy and flow cytometry. By switching to NIR irradiation, EGFR, CSPG4 anf CD44- expressing TNBC were selectively killed through induced phototoxic activities. Likewise, the1711(scFv)/αCSPG4(scFv)/αCD44(scFv)-SNAPf-AURIF immunoconjugates were able to selectively accumulate within targeted cells and significantly reduced cell viability through antimitotic activities at nano- to micromolar drug concentrations.

This study provides proof-of-concept for a future strategy to selectively destroy superficial light accessible EGFR, CSPG4 and CD44-expressing TNBC tumors and their metastatic lesions which are inaccessible to therapeutic light.

Biography: Dr. Fleury A. Nsole Biteghe is a lecturer under the MS in Biotechnology program at Northeastern University. He holds a PhD with specialization in Medical Biotechnology and Immunotherapy, from the University of Cape Town (UCT). As a postdoctoral scientist at Cedars Sinai hospital, he has contributed to elucidating immune resistant mechanisms causing immunotherapeutic treatment failures. He has over 12 years of academic and industrial research expertise focused on the development of antibody drug conjugates (ADCs) and photoconjugates (APCs) for photoimmunotherapeutic (PIT) application. Dr. Biteghe scientific efforts are focused on PIT, a novel light-dependent therapy utilizing the targeted binding of antibody-IR700 conjugate to a specific tumor antigen, with subsequent illumination, causing ROS production thereby inducing rapid cell death. After acquiring industry experience at Rakuten Medical and Takeda Oncology, Dr Biteghe joined Global Health Catalyst (GHC), an organization whose mission is to curb the growing cancer crisis and save millions of lives by catalyzing win-win collaborations for global health and innovation. Additionally, he is interested in developing the next generation of biotech entrepreneurs and improving biotech accessibility to underprivileged and historically disadvantaged communities, through his Nucleate activities. He has extensive experience in teaching biotechnology and enjoys translating his industry and research experience for academic application.