# Advancing Development of Novel Immunotherapy for Chemotherapy-induced Peripheral Neuropathy (CIPN)

> **NIH VA I01** · ALBUQUERQUE VA MEDICAL CENTER · 2024 · —

## Abstract

The opioid crisis has emphasized the need for better non-addictive therapeutics for pain management. The
chemotherapy-induced peripheral neuropathy (CIPN) imposed on approximately half of patients receiving
oxaliplatin treatment for cancer is a significant additional burden. While sophisticated molecular tools are now
being introduced to attack cancer and despite severe adverse effects, oxaliplatin chemotherapy remains in wide
usage as a primary treatment response at many sites. Its high prevalence of neurotoxicity often limits
chemotherapeutic dosing efficacy and maximum therapeutic effect. Patients can experience disabling cold and
mechanical hypersensitivity that persist for years after treatment. The toxic effects can cause premature
termination of treatment, impacting quality of life and survivability. CIPN can lead to permanent symptoms and
disability in up to 40% of cancer survivors subsequently, thus the societal loss in dollars is inestimable. There
are no drugs preventing development of CIPN, and CIPN has a poor therapeutic response to analgesics. Our
current collaborative effort focuses on optimizing a small molecule single chain Fragment variable antibody
(scFv) therapy that reverses chronic neuropathic pain. Smaller engineered scFvs (25-28 kDa) feature similar
binding activity but stronger tissue and brain penetrability. These small molecules are considered suitable drug
candidates for pain control since they satisfy key parameters such as (1) high affinity for the therapeutic target,
(2) high thermostability, (3) lack of aggregation, and (4) availability from high expression cell lines. Commercial
viability is dependent on humanization and affinity purification of the current patent pending small brain penetrant
scFv therapy effective in murine models. The objective of this proposal is to humanize the current small scFv
antibody and while maintaining more than 50% effectiveness in the murine CIPN pain model. The methodology
used will be to ascertain the minimum requirements for humanization, affinity maturation, and then to bench test
the antibody for effectiveness in the CIPN model vivo and in in vitro models including human-like neurons,
expression systems, and primary sensory neurons from CIPN mice to validate feasibility for continuing with
human clinical trials. Finally, we will seek independent commercial confirmation to demonstrate safety with
PK/PD, distribution, and toxicology validation studies. The ultimate objective of this project is realization of an
effective and commercially viable non-opioid treatment for chemotherapy induced neuropathic pain (CINP). The
single chain Fragment variable (scFv) antibody therapy designed would prevent CINP and/or mitigate long
standing, disabling CINP.

## Key facts

- **NIH application ID:** 10838358
- **Project number:** 5I01BX005937-02
- **Recipient organization:** ALBUQUERQUE VA MEDICAL CENTER
- **Principal Investigator:** KARIN N. WESTLUND-HIGH
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10838358

## Citation

> US National Institutes of Health, RePORTER application 10838358, Advancing Development of Novel Immunotherapy for Chemotherapy-induced Peripheral Neuropathy (CIPN) (5I01BX005937-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10838358. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*