A novel CD47-blocking peptide fused to pro-apoptotic KLA repeat inhibits lung cancer growth in mice
In this study, we identified a novel CD47-blocking peptide VK17 by phage display technique. A pro-apoptotic VK30 peptide was obtained after VK17 was fused to KLA amino acid repeat at C-termini. The VK30 was specifically bound to CD47 on lung cancer cells, and subsequently inducing lung cancer cell apoptosis. Meanwhile, the expression of Bax was increased, whereas the expression of Bcl-2 and Ki-67 were reduced in the VK30-treated lung cancer cells. In addition, VK30 effectively improved the phagocytic activity of macrophages against VK30-pretreated lung cancer cells. Combinational treatment of lung cancer cells with blockin...
Source: Cancer Immunology, Immunotherapy - October 13, 2023 Category: Cancer & Oncology Source Type: research
The influence of plasma sPD-L1 concentration on the effectiveness of immunotherapy in advanced NSCLC patients
ConclusionHigh sPD-L1 concentration is a negative predictor of immunotherapy efficacy in patients with NSCLC. It is worthwhile to determine sPD-L1 concentration to predict the risk of resistance to anti-PD-1 or anti-PD-L1 antibodies with greater certainty. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 10, 2023 Category: Cancer & Oncology Source Type: research
Translational development of a novel BAFF-R CAR-T therapy targeting B-cell lymphoid malignancies
In this study, we present the development of a novel CAR-T cell therapy targeting B-cell activating factor receptor (BAFF-R), a key regulator of B-cell proliferation and maturation. A new monoclonal antibody against BAFF-R was generated from a hybridoma clone and used to create a novel MC10029 CAR construct. Through a series of in vitro and in vivo models using the Nalm-6 cell line for leukemia and the Z138 cell line for lymphoma, we demonstrated the antigen-specific cytotoxicity of MC10029 CAR-T cells against tumor cells. Additionally, MC10029 CAR-T cells exhibited potent antitumor effects against CD19 knockout tumor cell...
Source: Cancer Immunology, Immunotherapy - October 10, 2023 Category: Cancer & Oncology Source Type: research
PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study
ConclusionNeoadjuvant therapy with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin showed promising efficacy and tolerability for larynx preservation in locally advanced laryngeal and hypopharyngeal SCC. The high response rates and favorable survival outcomes suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings and establish the role of immunotherapy in larynx preservation. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 7, 2023 Category: Cancer & Oncology Source Type: research
Intensified NK cell therapy in combination with low-dose chemoradiotherapy against human colorectal cancer
AbstractThe therapeutic potential of adoptive natural Killer (NK) cells immunotherapy in combination with chemoradiotherapy, the main treatment modality for colorectal cancer (CRC), has not yet been explored. Here, we aimed to investigate the efficacy of NK cells to potentiate primary tumor control and improve survival outcomes, especially in combination with low-dose chemoradiotherapy. Ex vivo activated NK cells (> 90% purity) from healthy donors were obtained. NK cells were administered intravenously to the CRC-bearing mice and intensified in vivo in combination with low-dose 5-fluorouracil (0.5 mg/kg or 1 mg/Kg)...
Source: Cancer Immunology, Immunotherapy - October 6, 2023 Category: Cancer & Oncology Source Type: research
Tumor-associated macrophages as a potential therapeutic target in thyroid cancers
AbstractMacrophages are important precursor cell types of the innate immune system and bridge adaptive immune responses through the antigen presentation system. Meanwhile, macrophages constitute substantial portion of the stromal cells in the tumor microenvironment (TME) (referred to as tumor-associated macrophages, or TAMs) and exhibit conflicting roles in the development, invasion, and metastasis of thyroid cancer (TC). Moreover, TAMs play a crucial role to the behavior of TC due to their high degree of infiltration and prognostic relevance. Generally, TAMs can be divided into two subgroups; M1-like TAMs are capable of d...
Source: Cancer Immunology, Immunotherapy - October 5, 2023 Category: Cancer & Oncology Source Type: research
An optimized protocol for the generation and monitoring of conditional orthotopic lung cancer in the KP mouse model using an adeno-associated virus vector compatible with biosafety level 1
ConclusionModifications to the anesthesia and instillation protocols increased the productivity of the original KP protocol. In addition, the switch to a gutless, adeno-associated, Cre-expressing vector allowed longitudinal monitoring of tumor growth under BSL-1 conditions, significantly reducing the number of animals required for an experiment, in line with the 3R principles. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 5, 2023 Category: Cancer & Oncology Source Type: research
ATOR-1017 (evunzekibart), an Fc-gamma receptor conditional 4-1BB agonist designed for optimal safety and efficacy, activates exhausted T cells in combination with anti-PD-1
ConclusionsThese preclinical data demonstrate a strong safety profile of ATOR-1017, together with its potent therapeutic effect as monotherapy and in combination with anti-PD1, supporting further clinical development of ATOR-1017. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 5, 2023 Category: Cancer & Oncology Source Type: research
Toxicity-specific peripheral blood T and B cell dynamics in anti-PD-1 and combined immune checkpoint inhibition
In conclusion, ICI-induced toxicity is dominated by enhanced Th1-associated responses, but in cICI we also found evidence for Th17-associated responses and germinal center activation. Together, our data add to the growing body of evidence that irAEs may be driven by newly activated CD4+ helper T cells, specifically after cICI. This study also supports tailored irAE treatment, based on ICI regimen, and to deploy specific strategies such as Th17 inhibition especially in cICI-associated irAEs.Graphical abstract (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 4, 2023 Category: Cancer & Oncology Source Type: research
Real-world cohort study of PD-1 blockade plus lenvatinib for advanced intrahepatic cholangiocarcinoma: effectiveness, safety, and biomarker analysis
ConclusionsPD-1 blockade plus lenvatinib is effective and safe in routine practice. PD-L1 expression and CA19-9 level appear to predict the treatment efficacy.IDH1 mutations might indicate a better treatment response.Clinical trial registration: NCT03892577. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - October 3, 2023 Category: Cancer & Oncology Source Type: research
Using patient-derived tumor organoids from common epithelial cancers to analyze personalized T-cell responses to neoantigens
AbstractAdoptive cell transfer of tumor-infiltrating lymphocytes (TIL) can mediate durable complete responses in some patients with common epithelial cancers but does so infrequently. A better understanding of T-cell responses to neoantigens and tumor-related immune evasion mechanisms requires having the autologous tumor as a reagent. We investigated the ability of patient-derived tumor organoids (PDTO) to fulfill this need and evaluated their utility as a tool for selecting T-cells for adoptive cell therapy. PDTO established from metastases from patients with colorectal, breast, pancreatic, bile duct, esophageal, lung, an...
Source: Cancer Immunology, Immunotherapy - September 8, 2023 Category: Cancer & Oncology Source Type: research
Decoding the genetic links between serum lipidomic profile, amino acid biomarkers, and programmed cell death protein-1/programmed cell death-ligand-1
ConclusionsThese findings provided new insights into the role of lipid metabolism as well as amino acids in regulating PD-1/PD-L1, suggesting that strategies targeting lipid and amino acid metabolisms may have therapeutic potential for improving the efficacy of immunotherapy. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 8, 2023 Category: Cancer & Oncology Source Type: research
Clinical trials of neoadjuvant immune checkpoint inhibitors for early-stage operable colon and rectal cancer
ConclusionHigh response rates from neoadjuvant ICI in early-stage colon and rectal cancer are reported in phase I/II studies. Contemporary trial designs are heterogeneous, with few comparable inclusion criteria, use of several drug combinations and durations and, wide variation of endpoints reported. Harmonizing clinical and translational aspects including survival data is needed for improved future trial designs with clinical impact. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 8, 2023 Category: Cancer & Oncology Source Type: research
Prognostic survival biomarkers of tumor-fused dendritic cell vaccine therapy in patients with newly diagnosed glioblastoma
AbstractDendritic cell (DC)-based immunotherapy has been applied to glioblastoma (GBM); however, biomarkers informing response remain poorly understood. We conducted a phase I/IIa clinical trial investigating tumor-fused DC (TFDC) immunotherapy following temozolomide-based chemoradiotherapy in patients with newly diagnosed GBM and determined prognostic factors in patients receiving TFDC immunotherapy. Twenty-eight adult patients with GBM isocitrate dehydrogenase (IDH) wild-type (IDH-WT) were enrolled; 127 TFDC vaccine injections (4.5 ± 2.6 times/patient) were administered. Patients with GBMIDH-WT had a respectable 5-...
Source: Cancer Immunology, Immunotherapy - September 8, 2023 Category: Cancer & Oncology Source Type: research
Previous radiotherapy improves treatment responses and causes a trend toward longer time to progression among patients with immune checkpoint inhibitor-related adverse events
ConclusionsBetter ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers. (Source: Cancer Immunology, Immunotherapy)
Source: Cancer Immunology, Immunotherapy - September 8, 2023 Category: Cancer & Oncology Source Type: research
