Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens.
Abstract
De novo immune responses to myeloid and other blood-borne tumors are notably limited and
ineffective, making our ability to promote immune responses with vaccines a major
challenge. While focus has been largely on cytotoxic cell-mediated tumor eradication,
B-cells and the antibodies they produce also have roles in anti-tumor responses. Indeed,
therapeutic antibody-mediated tumor cell killing is routinely employed in patients
with hematolymphoid cancers, but whether endogenous antibody responses can be incited
to blood-born tumors remains poorly studied. A major limitation of immunoglobulin
therapies is that cell surface expression of tumor-associated antigen (TAA) targets
is dynamic and varied, making promotion of polyclonal, endogenous B cell responses
appealing. Since many TAAs are self-antigens, developing tumor vaccines that enable
production of antibodies to non-polymorphic antigen targets remains a challenge. As
B cell responses to RNA vaccines are known to occur, we employed the Viral Replicon
Particles (VRP) which was constructed to encode mouse FLT3. The VRP-FLT3 vaccine provoked
a rapid IgG B-cell response to this self-antigen in leukemia and lymphoma mouse models.
In addition, IgGs to other TAAs were also produced. Our data suggest that vaccination
with RNA viral particle vectors incites a loss of B-cell tolerance that enables production
of anti-tumor antibodies. This proof of principle work provides impetus to employ
such strategies that lead to a break in B-cell tolerance and enable production of
broadly reactive anti-TAA antibodies as potential future therapeutic agents for patients
with hematolymphoid cancers.
Type
Journal articleSubject
AnimalsHumans
Mice
Alphavirus
Neoplasms
Immunoglobulin G
Cancer Vaccines
Viral Vaccines
Antigens, Neoplasm
Replicon
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https://hdl.handle.net/10161/25561Published Version (Please cite this version)
10.3389/fimmu.2022.865486Publication Info
Su, Hsuan; Imai, Kazuhiro; Jia, Wei; Li, Zhiguo; DiCioccio, Rachel A; Serody, Jonathan
S; ... Sarantopoulos, Stefanie (2022). Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG
to Murine Hematolymphoid Tumor Associated Antigens. Frontiers in immunology, 13. pp. 865486. 10.3389/fimmu.2022.865486. Retrieved from https://hdl.handle.net/10161/25561.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Jun Chen
Professor of Medicine
Phuong Linh Doan
Associate Professor of Medicine
Zhiguo Li
Associate Professor of Biostatistics & Bioinformatics
survival analysis, dynamic treatment regimes, clinical trials
Stefanie Sarantopoulos
Professor of Medicine
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