Clinical Trial

Disease: Non-small Cell Lung Cancer, NSCLC, (NCT05566223)

Disease info:

Lung cancer is generally divided into two types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), depending on the size of the affected cells when viewed under a microscope. NSCLC accounts for 85 % of all lung cancers, while SCLC accounts for the remaining 15 %.

Lung cancer may not cause signs or symptoms in its early stages. Some people with lung cancer have chest pain, frequent coughing, blood in the mucus, breathing problems, trouble swallowing or speaking, loss of appetite and weight loss, fatigue, or swelling in the face or neck. Additional symptoms can develop if the cancer spreads (metastasises) into other tissues.

NSCLC is divided into three main subtypes: adenocarcinoma, squamous cell carcinoma, and large cell lung carcinoma. Adenocarcinoma arises from the cells that line the small air sacs located throughout the lungs. Squamous cell carcinoma arises from squamous cells that line the passages leading from the windpipe to the lungs (bronchi). Large cell carcinoma arises from epithelial cells that line the lungs. Large cell carcinoma encompasses non-small cell lung cancers that do not appear to be adenocarcinomas or squamous cell carcinomas. The 5-year survival rate for people with NSCLC is usually between 11 and 17 %, but this can be lower or higher depending on the subtype and stage of the cancer.

Lung cancer is the second most common cancer in the United States. The American Cancer Society estimates approximately 238,340 new cases of lung cancer will be diagnosed in 2023.
Official title:
A Phase 1/2 Trial (CheckCell-2) in Patients With Metastatic Non-small Cell Lung Cancer (NSCLC) Administering Tumor-Infiltrating Lymphocytes (TILs) in Which the Gene Encoding CISH Was Inactivated Using the CRISPR/Cas9 System

Principal Investigator: Emil Lou, MD, PhD - Division of Hematology, Oncology, and Transplantation, University of Minnesota
Principal Investigator: Erminia Massarelli, MD, PhD, MS - Department of Medical Oncology & Therapeutics Research, City of Hope


United States, California

City of Hope Comprehensive Cancer Center, Duarte, California, United States, 91010


United States, Minnesota

Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States, 55455

Study start:
Nov. 25, 2022
70 participants
Gene editing method:
Type of edit:
Gene knock-out
Cytokine inducible SH2 containing protein (CISH)
Delivery method:
- Ex-vivo
IND Enabling Pre-clinical
Phase I Safety
Phase II Safety and Dosing
Phase III Safety and Efficacy

Status: Not yet recruiting


Tumor-infiltrating lymphocytes (TIL) have shown efficacy in certain cancers, principally in melanoma, but also in non-small cell lung cancer (NSCLC). Combination cell surface checkpoint inhibitor therapy has also been employed in an attempt to enhance the efficacy of these cell therapies. Genetic engineering of T cells to further increase anti-tumour activity is now possible. CISH (Cytokine-induced SH2 protein) is a novel intra-cellular immune checkpoint and an important negative regulator of T-cell signalling and function. The inhibition of CISH in mouse anti-tumour lymphocytes results in a marked increase in the ability of these lymphocytes to mediate tumour regression following administration to tumour-bearing mice. Additionally, data in genetically-engineered, neoantigen-specific human T cells in which CISH was inhibited, showed enhanced TCR functional avidity and increased ability of these T cells to detect cancer specific mutations and mount robust polyfunctional cytokine immune responses against their cognate cancer antigens. Thus, these T cells appear to have a significant advantage in inducing anti-tumour responses compared to wild-type anti-tumour lymphocytes. The researchers have developed and optimised a CRISPR-Cas9-based strategy for precise and efficient genetic engineering in primary human T cells without sacrificing cell viability or function, allowing for inhibition of a heretofore undruggable intracellular checkpoint. Thus, in this protocol, the researchers propose to inhibit the gene encoding the intracellular checkpoint target CISH in TILs from patients with metastatic NSCLC whose tumours are PD-L1 negative or positive, in order to evaluate the safety and efficacy of genetically engineered T cell therapy in the setting of novel checkpoint inhibition.

Last updated: Dec. 27, 2023
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