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

• 2022

Keyword

• hematolymphoid tumor
• VRP
• cancer vaccine
• antitumor antibody
• alphavirus replicon particle
• autoantigen
• B cell tolerance

DOI

• https://doi.org/10.17615/vj2z-mb53

Identifier

• https://dx.doi.org/10.3389/fimmu.2022.865486

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:

• Frontiers

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