Potential for Therapeutic Autovaccination Against Solid Tumors With Intratumoral Poly-ICLC

Get Permission

In a study reported in Cancer Immunology Research, Salazar and colleagues found a remarkable response to a strategy of sequential intratumoral and intramuscular injections of the stabilized dsRNA viral mimic and pathogen-associated molecular pattern (PAMP) polyinosinic-polycytidylic acid-polylysine-carboxymethylcellulose (poly-ICLC) in a patient with advanced facial embryonal rhabdomyosarcoma with extension to the brain. After treatment, the patient showed tumor inflammation consistent with immunotherapy followed by a gradual marked tumor regression and extended survival. The strategy, in which the sequential intratumoral and intramuscular injections mimic a viral infection, may allow “personalized systemic therapeutic ‘autovaccination’” against individual patient tumor antigens.

The investigators posit that the strategy comprises a three-step immunomodulatory process consisting of  (1) innate immune system local tumor killing induced by intratumoral poly-ICLC; (2) activation of dendritic cells with response weighted for Th1 cell and cytotoxic T lymphocyte priming against the tumor antigens released in response; and (3) maintenance of a systemic antitumor immune response via the intramuscular injections of poly-ICLC, including chemokine induction, facilitation of cytotoxic T-lymphocyte killing, inflammasome activation, and an increase in the T-effector/regulatory T-cell ratio.

They concluded, “These results support the use of certain simple and inexpensive [intratumoral] PAMPs to favorably stimulate effective immunity against solid cancers. A phase II clinical trial testing the hypothesis presented has begun accrual (clinicaltrials.gov, NCT01984892).” ■

Salazar AM, et al: Cancer Immunol Res 2:720-724, 2014.




By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.