Assessing Anti-B7-H3 Antibody and gp70 Cancer Vaccine Therapy for TNBC
Date
2022-04-18
Author
Advisors
Nair, Smita
Swartz, Adam
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Abstract
Immunotherapy has emerged as a promising approach for addressing TNBC, an aggressive
breast cancer subtype for which few targeted therapies exist. TNBC immunotherapy,
however, is dominated by PD-1 immune checkpoint blockade (ICB), which only benefits
a small minority of patients. To improve upon these initial efforts, we sought to
target B7-H3 with TNBC immunotherapy, as this marker is expressed in a vast majority
of TNBCs. In searching for an immunotherapy strategy, we decided to develop and assess
a B7-H3-targeting antibody with cancer vaccine combination, as this regimen has recently
shown resounding therapeutic benefits for another breast cancer type in the clinic
(NCT00524277). To this end, we adapted NCT00524277’s treatment components for murine
studies, creating M-m276, a B7-H3-targeting antibody, and a gp70-targeting cancer
vaccine; both B7-H3 and gp70 are human/mouse TNBC-specific biomarkers. M-m276 and
gp70 vaccine were administered in a B7-H3+ murine in vivo model of TNBC (i.e., Balb/C
mice with lung-seeded 4T1). Significant survival extension was observed in mice treated
with the combination therapy, relative to the monotherapies alone. Given these results,
we next sought to better understand the mechanism of this combination therapy. Upon
finding that M-m276 mediates antibody-dependent cellular phagocytosis (ADCP), we hypothesized
that M-m276 augments the efficacy of cancer vaccines by increasing tumor antigen presentation
to cytotoxic T lymphocytes (CTLs) through either cross-presentation or trogocytosis,
two ADCP-linked processes. Although M-m276 was found to have no impact on cross-presentation,
we found that M-m276 significantly increases the trogocytosis of tumor membrane by
antigen-presenting cells (APCs) in vitro, enabling these APCs to present greater amounts
of tumor antigen to CTLs. Altogether, our results support B7-H3-targeting antibody
with cancer vaccine as a TNBC treatment strategy and propose a potential mechanism
for how these therapy components interact.
Type
Honors thesisDepartment
BiologySubject
Cancer ImmunotherapyTriple-Negative Breast Cancer
Cancer Vaccine
Cancer Antibody
Antibody-Dependent Cellular Phagocytosis
Trogocytosis
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https://hdl.handle.net/10161/25108Citation
Sheu, Lauren (2022). Assessing Anti-B7-H3 Antibody and gp70 Cancer Vaccine Therapy for TNBC. Honors thesis, Duke University. Retrieved from https://hdl.handle.net/10161/25108.Collections
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Declaration of Ellen Matloff, Director of the Cancer Genetic Counseling Shared Resource at the Yale Cancer Center
Matloff, Ellen (2010-01-20)