Combination of Low-Dose Gemcitabine and PD-1 Inhibitors for Treatment in Patients With Advanced Malignancies.

Purpose: This study determined the efficacy of low-dose gemcitabine combined with programmed death-1 (PD-1) inhibitors for treating multiple malignancies, providing a cost-effective and safe treatment option.

Study Design: This study included 61 patients with advanced solid tumors treated with low-dose gemcitabine combined with PD-1 inhibitors at the Henan Cancer Hospital between January 2018 and February 2022. We retrospectively reviewed medical records to evaluate several clinical factors, including progression-free survival (PFS), overall survival (OS), adverse effects (AEs), and objective response to treatment.

Combining adoptive NK cell infusion with a dopamine-releasing peptide reduces senescent cells in aged mice.

Aging inducing the development of senescent cells (SNCs) in various tissues is considered as the main cause of the age-related diseases. Senotherapy has become a promising anti-aging therapy. However, the effectivity and side-effect of senolytic agents are still concern.

Phase I clinical trial of EGFR-specific CAR-T cells generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer patients.

Purpose: This phase I clinical trial is designed to assess the safety and feasibility of the epidermal growth factor receptor (EGFR) chimeric antigen receptor (CAR) T-cell generated by the piggyBac transposon system in advanced relapsed/refractory non-small cell lung cancer (NSCLC) patients. Compared to viral systems, the piggyBac transposon system is a simpler, more economical, and alternative way to introduce chimeric antigen receptor (CAR) transgenes into T cells.

Methods: This study recruited nine patients with advanced relapsed/refractory EGFR-positive NSCLC for two cycles of the piggyBac-generated EGFR-CAR T cells at dose of 1 × 10 cells/kg or 3 × 10 cells/kg of body weight.

Chimeric antigen receptor T cells engineered to secrete CD40 agonist antibodies enhance antitumor efficacy.

Background: Although chimeric antigen receptor (CAR)-T cell therapy has been remarkably successful for haematological malignancies, its efficacy against solid tumors is limited. The combination of CAR-T cell therapy with immune checkpoint inhibitors (CPIs), such as PD-1, PD-L1, and CTLA-4 antibodies, is a promising strategy for enhancing the antitumor efficacy of CAR-T cells. However, because most patients acquire resistance to CPIs, investigating other strategies is necessary to further improve the antitumor efficacy of CAR-T cell therapy for solid tumors.

Correction: Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Strategies for enrichment of circulating tumor cells.

Circulating tumor cells (CTCs) are cells derived from the primary sites of tumor patients into peripheral blood and serve as seeds that initiate tumor metastasis to distant sites. As a primary form of "liquid biopsy", CTC enumeration has exhibited great potential as a mean to obtain diagnostic and prognostic biomarker information in various cancers. The comprehensive clinical utility of CTC tests, however, is still restricted due to the scarcity and heterogeneity of CTCs, which necessitates reliable techniques for their efficient enrichment and characterization.

Current Progress in CAR-T Cell Therapy for Solid Tumors.

Cancer immunotherapy by chimeric antigen receptor-modified T (CAR-T) cells has shown exhilarative clinical efficacy for hematological malignancies. Recently two CAR-T cell based therapeutics, Kymriah (Tisagenlecleucel) and Yescarta (Axicabtagene ciloleucel) approved by US FDA (US Food and Drug Administration) are now used for treatment of B cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL) respectively in the US. Despite the progresses made in treating hematological malignancies, challenges still remain for use of CAR-T cell therapy to treat solid tumors.

Application of immune repertoire sequencing in cancer immunotherapy.

With the prominent breakthrough in the field of tumor immunology, diverse cancer immunotherapies have attracted great attention in the last decade. The immune checkpoint inhibitors, adoptive cell therapies, and therapeutic cancer vaccines have already achieved impressive clinical success. However, the fact that only a small subset of patients with specific tumor types can benefit from these treatments limits the application of cancer immunotherapy.

Modified CAR T cells targeting membrane-proximal epitope of mesothelin enhances the antitumor function against large solid tumor.

Mesothelin (MSLN) is an attractive antigen for chimeric antigen receptor (CAR) T therapy and the epitope selection within MSLN is essential. In this study, we constructed two types of CARs targeting either region I of MSLN (meso1 CAR, also known as a membrane-distal region) or region III of MSLN (meso3 CAR, also known as a membrane-proximal region) using a modified piggyBac transposon system. We reported that, compared with meso1 CAR T cells, meso3 CAR T cells express higher levels of CD107α upon activation and produce increased levels of interleukin-2, TNF-α, and IFN-γ against multiple MSLN-expressing cancer cells in vitro.

Detecting and phenotyping of aneuploid circulating tumor cells in patients with various malignancies.

Circulating tumor cells (CTCs) have been exclusively studied and served to assess the clinical outcomes of treatments and progression of cancer. Most CTC data have mainly been derived from distinct cohorts or selected tumor types. In the present study, a total of 594 blood samples from 479 cases with 19 different carcinomas and 30 healthy samples were collected and analyzed by Subtraction enrichment method combined with immunostaining-fluorescence in situ hybridization (iFISH).

Engineered CAR T cells targeting mesothelin by piggyBac transposon system for the treatment of pancreatic cancer.

Patients with pancreatic cancer have a poor prognosis largely due to the poor efficacy of the available treatment modalities. In this study, we engineered mesothelin-targeting chimeric antigen receptor T cells (mesoCAR T) using the piggyBac transposon based plasmid electroporation technique for specific targeting of pancreatic cancer cells expressing mesothelin. In vitro, mesoCAR T cells exhibited rapid and robust killing effect against ASPC1 cells with high expression levels of mesothelin with high production of IFN-γ; the cytotoxic effect on PANC1 cells with low expressions of mesothelin was relatively attenuated.

Cancer vaccine: learning lessons from immune checkpoint inhibitors.

Cancer vaccines have been exclusively studied all through the past decades, and have made exceptional achievements in cancer treatment. Few cancer vaccines have been approved by the US Food and Drug Administration (FDA), for instance, Provenge, which was approved for the treatment of prostate carcinoma in 2012. Moreover, more recently, T-VEC got approval for the treatment of melanoma.