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.