Undisclosed CISH inactivated TIL

The translation of CRISPR/Cas9-based CISH KO MR TIL from the basic research lab to current good manufacturing practices The (cGMP) facility was successful, allowing for optimized, large-scale expansion in support of a first-in-human clinical trial to treat patients with metastatic GI cancers (ClinicalTrials.gov Identifier: NCT04426669).

These results support the safety and potential antitumour activity of inhibiting the immune checkpoint CISH through the administration of neoantigen-reactive CISH-knockout TILs, with implications for patients with advanced metastatic cancers refractory to checkpoint inhibitor immunotherapies, and provide the first evidence that a novel intracellular checkpoint can be targeted with therapeutic effect.

P1/2, N=20, Active, not recruiting, Intima Bioscience, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Jan 2024 --> Jan 2026 | Trial primary completion date: Sep 2023 --> Jan 2026

Patients with prostate cancer (PC) generally do not respond favorably to immune checkpoint inhibitors, which may be due to a low abundance of tumor-infiltrating lymphocytes even when mutational load is high...Immune cell deconvolution suggested that the hot nodule was enriched not only in CD8+ and CD4 + T lymphocytes, but also in M1 macrophages, activated NK cells, and γδ T cells compared to the cold nodule. This case highlights that MMRd/TMB-high PC can evolve to minimize an anti-tumor immune response, and nominates downregulation of antigen presentation machinery (HLA loss) as a potential mechanism of adaptive immune evasion in PC.

This was a cooperative group, single-arm, phase 2 trial enrolling patients with unresectable mesothelioma after progression on more than or equal to one pemetrexed-containing regimen...Activation of tumor-infiltrating lymphocytes in response to treatment was associated with a trend toward improvement in PFS...Further investigation of this regimen in mesothelioma with nonepithelioid histology may be warranted. Clinical Trial Information: NCT03502746.

Past clinical trials of adjuvant therapy combined with interferon (IFN) alpha, fluorouracil, cisplatin, and radiation improved the 5-year survival rate of pancreatic ductal adenocarcinoma (PDAC)...Notably, IFN-OAd + chemotherapy + radiation remarkably suppressed tumor growth and induced a higher number of tumor-infiltrating lymphocytes without severe side toxic effects in an immunocompetent and adenovirus replication-permissive hamster PDAC model...IFN-OAd has the potential to overcome the barriers to clinical application of IFN-based therapy through its tumor-specific expression of IFN, induction of antitumor immunity, and sensitization with chemoradiation. Combining IFN-OAd with gemcitabine + nab-paclitaxel + radiation might be an effective and clinically beneficial treatment for PDAC patients.

High TMB has a prognostic role in resectable lung ADC. The high TMB group had a poor outcome with AC, suggesting that this group may be better served with immune checkpoint therapy.

Similar associations were observed between immune infiltrate and tumor phenotypes. Quantitative digital image analysis of the breast cancer microenvironment showed significant associations with demographic characteristics and biological indicators of aggressive behavior.

Currently, two patients have received TIL infusion without evidence of acute adverse toxicity related to the cellular product. Clinical updates will be presented.

We have enrolled over 40 women and have completed single cell RNA sequencing (scRNAseq), multiplex immunohistochemical assays, H&E scoring for tumor infiltrating lymphocytes (TILs) and NanoString molecular subtyping in 30 women... Single-cell RNA-seq is more reliable in identifying PD-1/ PD-L1 across cells than IHC assays. Single biomarker alone might not be predictive of treatment response. Our study is ongoing and we will categorize these patients into various subtypes based on presence or absence of multiple immune markers (PD-1/PDL-1, TILs, molecular subtypes, IHC assays) and will follow the disease course in these categories.