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

Publication ,  Journal Article
Su, H; Imai, K; Jia, W; Li, Z; DiCioccio, RA; Serody, JS; Poe, JC; Chen, BJ; Doan, PL; Sarantopoulos, S
Published in: Front Immunol
2022

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.

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Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2022

Volume

13

Start / End Page

865486

Location

Switzerland

Related Subject Headings

  • Viral Vaccines
  • Replicon
  • Neoplasms
  • Mice
  • Immunoglobulin G
  • Humans
  • Cancer Vaccines
  • Antigens, Neoplasm
  • Animals
  • Alphavirus
 

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Su, H., Imai, K., Jia, W., Li, Z., DiCioccio, R. A., Serody, J. S., … Sarantopoulos, S. (2022). Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens. Front Immunol, 13, 865486. https://doi.org/10.3389/fimmu.2022.865486
Su, Hsuan, Kazuhiro Imai, Wei Jia, Zhiguo Li, Rachel A. DiCioccio, Jonathan S. Serody, Jonathan C. Poe, Benny J. Chen, Phuong L. Doan, and Stefanie Sarantopoulos. “Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens.Front Immunol 13 (2022): 865486. https://doi.org/10.3389/fimmu.2022.865486.
Su, Hsuan, et al. “Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens.Front Immunol, vol. 13, 2022, p. 865486. Pubmed, doi:10.3389/fimmu.2022.865486.
Su H, Imai K, Jia W, Li Z, DiCioccio RA, Serody JS, Poe JC, Chen BJ, Doan PL, Sarantopoulos S. Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens. Front Immunol. 2022;13:865486.

Published In

Front Immunol

DOI

EISSN

1664-3224

Publication Date

2022

Volume

13

Start / End Page

865486

Location

Switzerland

Related Subject Headings

  • Viral Vaccines
  • Replicon
  • Neoplasms
  • Mice
  • Immunoglobulin G
  • Humans
  • Cancer Vaccines
  • Antigens, Neoplasm
  • Animals
  • Alphavirus