# Targeting the Chemokine System to Sensitize Tumors to Immunotherapy

> **NIH NIH P01** · ROSWELL PARK CANCER INSTITUTE CORP · 2020 · $2,808,311

## Abstract

The revised P01CA234212 tests novel strategies to promote selective CTL entry into tumor micro-
environments (TME) and sensitize “cold” tumors to immunotherapy. Our preclinical and early clinical data
demonstrate that the chemokine-modulating (CKM) regimen targeting toll-like receptor-3 (TLR3), type-1
interferons (IFN) and the PGE2 system, selectively enhances CTL numbers but reduces regulatory T(reg) cells
in TME, uniformly sensitizing tumors for the therapeutic effectiveness of PD-1 blockers and specialized
dendritic cell vaccines (αDC1) in melanoma, colorectal cancer (CRC) and ovarian cancer (OvCa). We will now:
1) Determine local immunologic efficacy of systemically- or locally applied CKMs in cancer patients; 2) Identify
the most effective ways of using CKM to enhance antitumor effects DC therapies and PD-1 blockade; and 3)
Evaluate the clinical activity of the resulting therapies in PD-1-resistant cancer patients, and identify the most
relevant TME correlates of clinical benefit.
Project 1 Combinatorial adjuvants promote uniform and selective intratumoral CTL infiltration will test
in a Phase IIa trial NCT03403634 whether systemic administration of CKM composed of rintatolimod (TLR3-
ligand) IFNα and celecoxib promotes local CTL accumulation in TME of metastatic colorectal cancer (CRC).
Magnitude of effects, tumor-selectivity (vs surrounding tissues) and mouse studies will guide the design of the
second trial which will evaluate the clinical efficacy of sequential CMK/anti-PD-1 application in CRC patients.
Project 2 Local immunotherapy corrects chemokine patterns in OvCa will complete the phase II portion of
trial NCT02432378 to test the specificity of local CKM in attracting CTLs (rather than Tregs) to the TME of
OvCa patients vaccinated with αDC1 loaded with own tumor cells (αDC1[tumor]) and identify “secondary”
mechanisms or treatment resistance. The results will inform preclinical studies and the design of the second
trial to determine the clinical activity of sequential treatment with DC[tumor]/CKM followed with PD-1 blockade.
Project 3 Chemokine modulation to enhance CD8+ TIL recruitment and cross-priming in the TME is
based on our latest observations (NCT01876212) of 57% objective response rate (ORR) to αDC1 vaccine
targeting tumor blood vessels (αDC1[TBVA] in the 4 of 7 melanoma patients with primary PD1 resistance and
46% objective clinical benefit overall (6/13 patients). We will now perform phase II trial to evaluate the clinical
activity of αDC1[DBVA] combined with systemic CKM (BB-IND16,704) in stage IV melanoma patients with
primary PD1 resistance. Using correlative studies and mouse in vivo models, we will develop optimized and
potentially simplified vaccines to complement CKM and PD-1 blockade for durable therapeutic benefit.
Impact: We will test widely-applicable complementary approaches to promote selective entry of therapeutic
CTLs into tumors. Since intratumoral CTL numbers predict survival and therapeutic advantage of c...

## Key facts

- **NIH application ID:** 9869513
- **Project number:** 1P01CA234212-01A1
- **Recipient organization:** ROSWELL PARK CANCER INSTITUTE CORP
- **Principal Investigator:** Pawel Kalinski
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,808,311
- **Award type:** 1
- **Project period:** 2020-03-03 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869513

## Citation

> US National Institutes of Health, RePORTER application 9869513, Targeting the Chemokine System to Sensitize Tumors to Immunotherapy (1P01CA234212-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9869513. Licensed CC0.

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