# Development of a patient-derived organotypic spheroids (PDOTS) platform for prediction of clinical responses to immuno-oncology drugs

> **NIH NIH R43** · XSPHERA BIOSCIENCES INCORPORATED · 2021 · $381,800

## Abstract

ABSTRACT
As many new immuno-oncology (IO) therapies for cancer are developed, oncologists will be faced with the
challenge of choosing from hundreds of drugs with thousands of potential combinations to treat their patients.
Xsphera Biosciences Inc. (XB) believes one solution to this challenge lies in a novel combination of a tumor
processing method that produces patient-derived organotypic tumor spheroids (PDOTS) and a microfluidic
device that preserves the tumor microenvironment of a patient’s tumor. XB aims to develop the PDOTS platform
to 1) provide oncologists with data-driven treatment options for their patients and 2) provide biopharmaceutical
companies with data that will de-risk IND initiation by reliably predicting patient clinical responses to IO and
chemotherapeutic drugs. One of the key actions needed is a systematic evaluation and optimization of the
different classes of immunotherapeutic drugs in the platform. These classes include, but are not limited to, tumor
cell-targeted IgG1 antibodies (tumor-targeted Abs), checkpoint inhibitors, gene therapy, and cell therapy
including chimeric antigen receptor T-cell therapy (CAR-T).
This project aims to establish the parameters to test tumor-targeted Ab therapeutics in the Xsphera platform and,
using cetuximab in colorectal cancer (CRC), confirm that the efficacy of cetuximab aligns with the historical
clinical experience.
Specific Aim 1 will characterize the effects of cetuximab on CRC PDOTS in the Xsphera platform and determine
if the ex vivo responses in RAS wild type (RASwt) and RAS mutant tumors (RASmut) are consistent with those
reported in the clinic. Cetuximab is indicated for RASwt but has shown no efficacy in tumors with RASmut.The
immune activation in the PDOTS induced by cetuximab will be characterized, and the cytokine and gene
expression profiles for immune activation and apoptosis will be measured and correlated with cytotoxicity data.
Specific Aim 2 will characterize the kinetics of Ab-mediated immune activation to establish the optimal time to
monitor cytotoxicity and immune activation signals. Using the dose of cetuximab that induced the highest level
of cytotoxicity, the kinetics of Ab mediated cytotoxicity and immune modulation will be characterized during the
first 3 days after Ab treatment. The timepoint with the highest cytotoxicity and immune modulatory signals and
the lowest variability between replicates and between patients will support standardization on the timepoint for
cetuximab treatment. Specific Aim 2 will further characterize the immune involvement by mAb neutralization of
known immune effector mechanisms, including NK cells, CTL cells and the complement cascade.
Results of Phase I will confirm whether clinically approved cetuximab is effective in the platform by quantifying
cytotoxicity and characterizing immune activation and whether it aligns with historical clinical response data and
for being restricted to RASwt.

## Key facts

- **NIH application ID:** 10324751
- **Project number:** 1R43CA261382-01A1
- **Recipient organization:** XSPHERA BIOSCIENCES INCORPORATED
- **Principal Investigator:** Amir Reza Aref
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $381,800
- **Award type:** 1
- **Project period:** 2021-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10324751

## Citation

> US National Institutes of Health, RePORTER application 10324751, Development of a patient-derived organotypic spheroids (PDOTS) platform for prediction of clinical responses to immuno-oncology drugs (1R43CA261382-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10324751. Licensed CC0.

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