Learning from viruses: the necrotic bodies of tumor cells with intracellular synthetic dsRNA induced strong anti-tumor immune responses.
OBJECTIVE
Coaxing dead tumor cells to induce specific immune responses is an attractive tumor therapy. However, there continues to be a need for adjuvants that can promote the cross-presentation of the dead tumor cells to induce specific anti-tumor response. Viral dsRNA has multiple mechanisms to promote the cross-presentation of viral antigens in virus-infected cells. We propose to learn from viruses by generating dead tumor cells having synthetic dsRNA delivered inside them to allow the dsRNA to promote the cross-presentation of dead tumor cells.


METHODS
Using synthetic dsRNA, poly(I:C), and the TC-1 cervical cancer model, we evaluated the extent to which the poly(I:C) can promote the necrotic bodies of TC-1 cells to induce specific anti-tumor immune response. The poly(I:C) was either simply mixed with the dead TC-1 cells or pre-loaded inside them.


RESULTS
Immunization of tumor-bearing mice with the necrotic bodies of tumor cells admixed with poly(I:C) significantly inhibited the tumor growth. More importantly, immunization with the necrotic bodies having poly(I:C) pre-loaded inside led to a significantly stronger anti-tumor response than when the necrotic bodies were simply admixed with the poly(I:C), apparently through a CD8(+) CTL response-mediated mechanism.


CONCLUSIONS
These findings are expected to be clinically relevant for devising improved whole cell-based tumor vaccines.
Cui
Zhengrong
Z
Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, OR 97331, USA. zhengrong.cui@oregonstate.edu
Le
Uyen M
UM
Qiu
Fu
F
Shaker
Dalia S
DS
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D005260:Female; D007114:Immunization; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D009374:Neoplasms, Experimental / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000276:Adjuvants, Immunologic; D012330:RNA, Double-Stranded; D011070:Poly I-C