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

Downloadable Content

Download PDF
Creator
  • Su, Hsuan
    • Other Affiliation: Duke University Medical Center
  • Imai, Kazuhiro
    • Other Affiliation: Duke University Medical Center
  • Jia, Wei
    • Other Affiliation: Duke University Medical Center
  • Li, Zhiguo
    • Other Affiliation: Duke University Medical Center
  • DiCioccio, Rachel A.
    • Other Affiliation: Duke University Medical Center
  • Serody, Jonathan S.
    • Affiliation: School of Medicine, Department of Medicine
  • Poe, Jonathan C.
    • Other Affiliation: Duke University Medical Center
  • Chen, Benny J.
    • Other Affiliation: Duke University Medical Center
  • Doan, Phuong L.
    • Other Affiliation: Duke University Medical Center
  • Sarantopoulos, Stefanie
    • Other Affiliation: Duke University Medical Center
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.
Date of publication
Keyword
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
License
  • Attribution 4.0 International
Journal title
  • Frontiers in Immunology
Journal volume
  • 13
Language
  • English
Version
  • Publisher
ISSN
  • 1664-3224
Parents:

This work has no parents.

In Collection:

Items