Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens.

Su, Hsuan

Imai, Kazuhiro

Jia, Wei

Li, Zhiguo

DiCioccio, Rachel A

Serody, Jonathan S

Poe, Jonathan C

Chen, Benny J

Doan, Phuong L

Sarantopoulos, Stefanie

2022-08-01T20:36:23Z

2022-08-01T20:36:23Z

2022-01

2022-08-01T20:36:20Z

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.

1664-3224

1664-3224

https://hdl.handle.net/10161/25561

eng

Frontiers Media SA

Frontiers in immunology

10.3389/fimmu.2022.865486

Animals

Humans

Mice

Alphavirus

Neoplasms

Immunoglobulin G

Cancer Vaccines

Viral Vaccines

Antigens, Neoplasm

Replicon

Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens.

Journal article

Li, Zhiguo|0000-0002-9975-6005

Chen, Benny J|0000-0003-4588-3890

Doan, Phuong L|0000-0003-1361-2068

865486

Duke

School of Medicine

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Biostatistics & Bioinformatics

Medicine

Duke Cancer Institute

Regeneration Next Initiative

Medicine, Hematologic Malignancies and Cellular Therapy

Published

13