# Early development of small molecule dendritic cell immunopotentiators for the treatment of solid tumors

> **NIH NIH R01** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2021 · $370,994

## Abstract

Summary
The critical role of the innate immune system in priming CD8+ T cells to generate tumor specific responses
underscores a potentially important clinical strategy for the development of next-generation immunotherapies. In
this proposal, we pursue the hypothesis that small molecules identified in a high throughput screen for innate
immune agonists can significantly improve the therapeutic efficacy of the oncolytic NDV (NewCastle Disease
Virus) through activation of antigen presenting cells (APCs), and enhancement of anticancer immune responses.
To address this, we propose specific aims that focus on hit validation through both ex vivo and in vivo
characterization of compounds and assessing the in vivo efficacy in a B16-F10 mouse melanoma model. First,
utilizing orthogonal assays, we will validate the immunopotentiation properties of compounds in ex vivo human
primary monocyte derived dendritic cell (MDDC). Specifically, we propose to assess compound effects on
MDDC activation and maturation through examination of transcriptional profiles, expression of DC activation
markers, and cytokines being secreted upon compound treatment. Validated hits will then be clustered based
on their activities, and the most potent compounds from each cluster will be carried forward to anti-tumor efficacy
testing in a mouse melanoma model. Compounds will be added either alone or together with intratumoral
injection of oncolytic NDV. Compound that synergize and enhance the anti-tumor activity of NDV, provide durable
protection, and abscopal activity will be prioritized for subsequent early lead optimization.
 Based on data generated from these hit validation approaches, we propose to delineate ex vivo immune
signatures that can be used as surrogates for in vivo efficacy. The immune signatures elicited by selected hits
within both MDDCs (ex vivo) and the tumor microenvironment (TME - in vivo) will be integrated to construct a
computational model to assess correlative signatures that are able to link MDDC molecular and phenotypic
responses to in vivo efficacy. Similar analysis will be conducted on immune activation readouts in the TME. This
will be a reiterative process, with information obtained from the experimental studies will be utilized to refine
predictions of ex vivo and in vivo biomarkers that correlate with efficacy. The information gained from this
proposed study upon completion will significantly facilitate further hit-to-lead and lead optimization activities
during subsequent phases of the drug development process.

## Key facts

- **NIH application ID:** 10180915
- **Project number:** 5R01CA229818-04
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** SUMIT K CHANDA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $370,994
- **Award type:** 5
- **Project period:** 2018-07-11 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180915

## Citation

> US National Institutes of Health, RePORTER application 10180915, Early development of small molecule dendritic cell immunopotentiators for the treatment of solid tumors (5R01CA229818-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10180915. Licensed CC0.

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