Home » Key Clinical Research Articles Global Medical Discovery » Therapeutic in situ autovaccination against solid cancers with intratumoral poly-ICLC: case report, hypothesis, and clinical trial.

Therapeutic in situ autovaccination against solid cancers with intratumoral poly-ICLC: case report, hypothesis, and clinical trial.

Significance Statement

We propose that the encouraging therapeutic response to comprehensive innate and adaptive immune activation with sequential intratumoral and intramuscular Hiltonol® (poly-ICLC) in a volunteer patient with an advanced rhabdomyosarcoma, together with the scientific background underlying his treatment, provides encouraging evidence of the potential for a relatively simple, safe and inexpensive, yet potent approach to cancer immunotherapy that essentially converts the tumor into its own personalized vaccine.  An ongoing clinical trial based on this strategy is briefly described. Conclusion: Sequential IT and IM Hiltonol® (Poly-ICLC) injections mimicking a viral infection can induce an 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 intratumoral Hiltonol; 2) Th1-and cytotoxic lymphocyte (CTL)-weighted priming against released tumor antigens as mediated by Hiltonol activated mDC; and 3) IM Hiltonol maintenance of the systemic anti-tumor immune response. This includes migration of anti-tumor CTL to remote metastases via chemokine induction, facilitation of CTL action via induction of costimulators such as OX40, inflammasome activation, and increase in the T-effector/Treg ratio by Hiltonol. Results support use of certain simple and inexpensive IT pathogen associated molecular patterns (PAMPs) to favorably stimulate effective immunity against solid cancers.  A small pilot clinical trial to evaluate the hypothesis presented has begun accruals (clinicaltrials.gov, NCT01984892), and a larger multicenter phase II trial in patients with melanoma, sarcoma, head and neck cancers and skin cancers will begin in Jan, 2015.

Therapeutic in situ autovaccination against solid cancers with intratumoral poly-ICLC: case report, hypothesis, and clinical trial.. Global Medical Discovery

 

 

 

Salazar AM1, Erlich RB2, Mark A3, Bhardwaj N4, Herberman RB5. Cancer Immunol Res. 2014 ;2(8):720-4.

1Oncovir, Inc., Washington, District of Columbia; [email protected]

2Bay Hematology-Oncology, Easton;and

3Bethesda MRI, Bethesda, Maryland; and.

4Icahn School of Medicine at Mount Sinai, New York, New York.and

5Oncovir, Inc., Washington, District of Columbia;

Abstract

 Pathogen-associated molecular patterns (PAMP) are stand-alone innate and adaptive immunomodulators and critical vaccine components. We present a strategy of sequential  intratumoral  (i.t.) and intramuscular (i.m.) injections of the stabilized dsRNA viral mimic and PAMP, polyinosinic-polycytidylic acid-polylysine-carboxymethylcellulose (poly-ICLC, Hiltonol; Oncovir). We report the first treated patient, a young man with an exceptionally advanced facial embryonal rhabdomyosarcoma with extension to the brain. After treatment, the patient showed tumor inflammation consistent with immunotherapy, followed by gradual, marked tumor regression, with extended survival. Sequential i.t. and i.m. poly-ICLC injections mimicking a viral infection can induce an effective, in situ, personalized systemic therapeutic  “autovaccination” against tumor antigens of a patient. We postulate a three-step immunomodulatory process: (i) innate-immune local tumor killing induced by i.t. poly-ICLC; (ii) activation of dendritic cells with Th1 cell- and CTL-weighted priming against the released tumor antigens; and (iii) i.m. poly-ICLC maintenance of the systemic antitumor immune response via chemokine induction, facilitation of CTL killing through the induction of costimulators such as OX40, inflammasome activation, and increase in the T-effector/Treg ratio. These results support the use of certain simple and inexpensive i.t. PAMPs to favorably stimulate effective immunity against solid  cancers. A phase II clinical trial testing the hypothesis presented has begun accrual (clinicaltrials.gov, NCT01984892).

©2014 American Association for Cancer Research.

Go To Cancer Immunol. Res.