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Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in gastric, breast, and lung cancer. We characterized the molecular subtypes of non-small cell lung cancer (NSCLC) expressing KK-LC-1 to inform rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. 9790 NSCLC tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median, 3.25 vs. 1.17 transcripts per million (TPM), p < 0.0001). Tumors with the highest quartile of KK-LC-1 expression had a greater proportion of tumors with high tumor mutation burden (TMB) (≥10 mutations per megabase; 44% vs. 28% in Q1, p < 0.001). Increased KK-LC-1 expression was associated with increased M1 macrophage abundance. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with high TMB. TCR-T therapy directed against KK-LC-1 should be considered in patients whose clinical features reflect these characteristics.

Purpose: To explore valuable predictors for mediastinal lymph node metastasis in non-small cell lung cancer (NSCLC) patients, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from preoperative 18F-FDG PET/CT combined with clinical characteristics. Methods: Data from 224 NSCLC patients who underwent preoperative 18F-FDG PET/CT scans in our hospital were collected. Then, a series of clinical parameters including SUV-derived features [SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] were evaluated. The best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Predictive analyses were performed using a Logistic regression model to determine the predictive factors for mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. After multivariate model construction, data of another 100 NSCLC patients were recorded. Then, 224 patients and 100 patients were enrolled to validate the predictive model by the area under the receiver operating characteristic curve (AUC). Results: The mediastinal lymph node metastasis rates in 224 patients for model construction and 100 patients for model validation were 24.1% (54/224) and 25% (25/100), respectively. It was found that SUVmax of mediastinal lymph node ≥ 2.49, primary-tumor SUVmax ≥ 4.11, primary-tumor SUVpeak ≥ 2.92, primary-tumor SUVmean ≥ 2.39, primary-tumor MTV ≥ 30.88 cm3, and primary-tumor TLG ≥ 83.53 were more prone to mediastinal lymph node metastasis through univariate logistic regression analyses. The multivariate logistic regression analyses showed that the SUVmax of mediastinal lymph nodes (≥ 2.49: OR 7.215, 95% CI 3.326–15.649), primary-tumor SUVpeak (≥ 2.92: OR 5.717, 95% CI 2.094–15.605), CEA (≥ 3.94 ng/ml: OR 2.467, 95% CI 1.182–5.149), and SCC (< 1.15 ng/ml: OR 4.795, 95% CI 2.019–11.388) were independent predictive factors for lymph node metastasis in the mediastinum. It was found that SUVmax of the mediastinal lymph node (≥ 2.49: OR 8.067, 95% CI 3.193–20.383), primary-tumor SUVpeak (≥ 2.92: OR 9.219, 95% CI 3.096–27.452), and CA19-9 (≥ 16.6 U/ml: OR 3.750, 95% CI 1.485–9.470) were significant predictive factors for mediastinal lymph node metastasis in lung adenocarcinoma patients. The AUCs for the predictive value of the NSCLC multivariate model through internal and external validation were 0.833 (95% CI 0.769- 0.896) and 0.811 (95% CI 0.712–0.911), respectively. Conclusion: High SUV-derived parameters (SUVmax of mediastinal lymph node and primary-tumor SUVmax, SUVpeak, SUVmean, MTV and TLG) might provide varying degrees of predictive value for mediastinal lymph node metastasis in NSCLC patients. In particular, the SUVmax of mediastinal lymph nodes and primary-tumor SUVpeak could be independently and significantly associated with mediastinal lymph node metastasis in NSCLC and lung adenocarcinoma patients. Internal and external validation confirmed that the pretherapeutic SUVmax of the mediastinal lymph node and primary-tumor SUVpeak combined with serum CEA and SCC can effectively predict mediastinal lymph node metastasis of NSCLC patients. [ABSTRACT FROM AUTHOR]

We report the synthesis and biological evaluation of 131I‐labeled antihuman tumor‐derived immunoglobulin G (IgG) light chain monoclonal antibody (4E9) ([131I]I‐4E9) as a promising probe for tumor imaging. [131I]I‐4E9 was synthesized in radiochemical yield of 89.9 ± 4.7% with radiochemical purity of more than 99%. [131I]I‐4E9 showed high stability in normal saline and human serum. In cell uptake studies, [131I]I‐4E9 exhibited favorable binding affinity and high specificity in HeLa MR cells. In biodistribution studies, [131I]I‐4E9 showed high tumor uptake, high tumor/non‐tumor ratios, and specific binding in BALB/c nu/nu mice bearing human HeLa MR xenografts. Single‐photon emission computerized tomography (SPECT) imaging of [131I]I‐4E9 in the HeLa MR xenograft model demonstrated clear visualization of tumor after 48 h and confirmed specific binding in tumor. These findings suggest that [131I]I‐4E9 possesses favorable biological characteristics and warrants further investigation as a prospective probe for imaging and treatment of cancers. [ABSTRACT FROM AUTHOR]

Radioimmunotherapy (RIT) has great potential in cancer therapy. However, its efficacy in numerous tumors is restricted due to myelotoxicity, thereby limiting the dose of radionuclide. To increase tumor radiosensitivity, we incorporated the recombinant lentivirus into the EJ cells (bladder cancer [BC] cells), and examined the combined anti-tumor effects of RIT with 131I-BDI-1(131I-monoclonal antibody against human BC-1) and gene therapy (GT). The recombinant lentivirus was constructed and packed. The animal xenograft model was built and when the tumor reached about 0.5 cm in diameter, the mice were randomly separated into four groups: (1) RIT + GT: the xenografts were continuously incorporated with the recombinant lentivirus for two days. And 7.4 MBq 131I-BDI-1 was IV-injected, and 10 mg prodrug 5-fluorocytosine (FC) was IV-injected for 7 days, (2) RIT: same dose of 131I-BDI-1 as the previous group mice, (3) GT: same as the first group, except no 131I-BDI-1, and (4) Untreated. Compute tumor volumes in all groups. After 28 days the mice were euthanized and the tumors were extracted and weighed, and the inhibition rate was computed. The RIT + GT mice, followed by the RIT mice, exhibited markedly slower tumor growth, compared to the control mice. The tumor size was comparable between the GT and control mice. The tumor inhibition rates after 28 days of incubation were 42.85 ± 0.23%, 27.92 ± 0.21% and 0.57 ± 0.11% for the four groups, respectively. In conclusion, RIT, combined with GT, suppressed tumor development more effectively than RIT or GT alone. This data highlights the potent additive effect of radioimmune and gene therapeutic interventions against cancer. [ABSTRACT FROM AUTHOR]