Pathogen associated molecular patterns (PAMPs) are standalone innate and adaptive immunomodulators and critical vaccine components. We present a strategy of sequential intratumoral (IT) and intramuscular (IM) injections of the stabilized dsRNA viral mimic and PAMP, poly-inosinic-polycytidylic acid-poly-lysine-carboxymethylcellulose (poly-ICLC, Hiltonol®). We report the first treated patient, a young man with an exceptionally advanced facial embryonal rhabdomyosarcoma with extension to brain. The patient showed tumor inflammation consistent with immunotherapy, followed by gradual marked tumor regression, with extended survival. Sequential IT and IM Poly-ICLC injections mimicking a viral infection can induce an effective, in-situ, personalized systemic therapeutic 'autovaccination' against a patient's individual tumor antigens. We postulate a three-step immunomodulatory process: 1) innate-immune local tumor killing induced by IT poly-ICLC; 2) Activation of dendritic cells with Th1 and cytotoxic lymphocyte (CTL)-weighted priming against released tumor antigens; and 3) IM Poly-ICLC maintenance of the systemic anti-tumor immune response via chemokine induction, facilitation of CTL killing through induction of costimulators such as OX40, inflammasome activation, and increase in the T-effector/Treg ratio. Results support use of certain simple and inexpensive IT PAMPs to favorably stimulate effective immunity against solid cancers. A phase II clinical trial testing the hypothesis presented has begun accruals. (clinicaltrials.gov, NCT01984892)
- Received February 17, 2014.
- Revision received April 22, 2014.
- Accepted April 22, 2014.
- Copyright © 2014, American Association for Cancer Research.