Personalized Dendritic-cell-based Vaccines Targeting Cancer Neoantigens.

Cancer immunotherapy activates the host immune system against tumor cells and has the potential to lead to the development of innovative strategies for cancer treatment. Neoantigens are non-self-antigens produced by genetic mutations in tumor cells that induce a strong immune response against tumor cells without central immune tolerance. Along with advances in neoantigen analysis technology, the development of vaccines focusing on neoantigens is being accelerated.

A pilot study on the safety and efficacy of neoadjuvant chemo‑adoptive immunotherapy for locally advanced rectal cancer.

The safety and efficacy of combination therapy of immune cell therapy and chemotherapy [chemo-adoptive immunotherapy (CAIT)] for patients with stage IV or recurrent colorectal cancer have been reported. In the present study, the safety and efficacy of neoadjuvant CAIT were investigated for preoperative therapy of locally advanced rectal cancer. The study included patients with cT3/T4 or cN (+) rectal adenocarcinoma scheduled for curative surgery.

Effects of adoptive T-cell immunotherapy on immune cell profiles and prognosis of patients with unresectable or recurrent cholangiocarcinoma.

The identification of immune cell profiles (ICP) involved in anti-tumor immunity is crucial for immunotherapy. Therefore, we herein investigated cholangiocarcinoma patients (CCA) who received adoptive T-cell immunotherapy (ATI). Eighteen unresectable or recurrent CCA received ATI of αβ T cells alone or combined with chemotherapy.

Safety evaluation of immune-cell therapy for malignant tumor in the Cancer Immune-cell Therapy Evaluation Group (CITEG).

Background Aims: With the aim of strengthening the scientific evidence of immune-cell therapy for cancer and further examining its safety, in October 2015, our hospital jointly established the Cancer Immune-Cell Therapy Evaluation Group (CITEG) with 39 medical facilities nationwide.

Methods: Medical information, such as patients' background characteristics, clinical efficacy and therapeutic cell types obtained from each facility, has been accumulated, analyzed and evaluated by CITEG. In this prospective study, we analyzed the adverse events associated with immune-cell therapy until the end of September 2022, and we presented our interim safety evaluation.

Efficacy of Adjuvant Immune-cell Therapy Combined With Systemic Therapy for Solid Tumors.

Background/aim: The efficacy of adjuvant systemic therapy after surgical resection remains unsatisfactory; therefore, a new treatment strategy is required. We aimed to examine the efficacy of adjuvant immune-cell therapy using activated T lymphocytes with or without dendritic cell vaccination in combination with standard adjuvant systemic therapies in terms of the survival of patients with solid tumors, such as lung, gastric, pancreatic, colorectal, and breast cancers.

Patients And Methods: A total of 141 patients with solid tumors were enrolled in this study.

Prognostic Factors for Advanced/Recurrent Breast Cancer Treated With Immune-cell Therapy.

Background/aim: Advanced/recurrent breast cancer (ARBC) still has a poor prognosis; therefore, new treatment strategies are required. In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy using T lymphocytes activated in vitro with or without dendritic cell vaccination in combination with standard therapies in terms of the survival of patients with ARBC.

Patients And Methods: A total of 127 patients with ARBC were enrolled in this study.

Esophageal cancer responsive to the combination of immune cell therapy and low-dose nivolumab: two case reports.

Background: Blocking the programmed death 1 pathway by immune checkpoint inhibitors induces dramatic antitumor activity in patients with malignant tumors. However, the clinical response to immune checkpoint inhibitors remains limited owing to the patients' immunological status, such as the number of lymphocytes, programmed death ligand 1 expression, and tumor mutation burden. In this study, we successfully treated two patients with advanced esophageal cancer who responded to the combination of adoptive immune cell therapy and a low-dose immune checkpoint inhibitor, nivolumab.

Effect of adoptive T-cell immunotherapy on immunological parameters and prognosis in patients with advanced pancreatic cancer.

Background Aims: Immunotherapy is effective for many types of cancer, but its benefits in advanced pancreatic cancer, which has a poor prognosis, are not well established. In this study, the authors examined the effects of adoptive T-cell immunotherapy (ATI) on immune cell profiles and prognosis in patients with unresectable advanced pancreatic cancer.

Methods: Seventy-seven patients with unresectable advanced pancreatic cancer were treated with six cycles of αβ T cells alone or in combination with chemotherapy or chemoradiation.

Changes in Immunological Status in Patients With Metastatic Colorectal Cancer Treated With First-line Chemoimmunotherapy.

Background/aim: Chemoimmunotherapy is a promising treatment for various malignant diseases. In this study, we examined whether first-line chemoimmunotherapy using adoptive immune-cell therapy was effective for metastatic colorectal cancer (mCRC).

Patients And Methods: The therapeutic efficacy and safety of the standard first-line chemoimmunotherapy with adoptive αβ T cell therapy and bevacizumab were assessed using thirty-two patients with mCRC in our hospital.

Adoptive Immune-Cell Therapy for the Treatment of Neuroendocrine Carcinoma of the Uterine Cervix.

Background/aim: We aimed to investigate the efficacy of immune-cell therapy in terms of the survival of patients with neuroendocrine carcinoma of the uterine cervix (NECC), which lacks standardized therapeutic approaches.

Patients And Methods: We identified 17 patients who were diagnosed as having NECC and treated with immune-cell therapy. The clinical characteristics of these patients were extracted from their records and their overall survival was measured.

Prognostic Factors for Endometrial and Cervical Cancers of Uterus Treated With Immune-cell Therapy: A Retrospective Study.

Background/aim: In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy using T lymphocytes activated in vitro with or without dendritic cell vaccination in combination with standard therapies in terms of the survival of patients with advanced or recurrent endometrial and cervical cancers of the uterus.

Patients And Methods: A total of 187 patients with advanced or recurrent uterine cancer were enrolled in this study. The correlation between overall survival and various clinical factors was examined by univariate and multivariate analyses.

Effects of adaptive immune cell therapy on the immune cell profile in patients with advanced gastric cancer.

Background: Immunotherapy for cancer patients has been the subject of attention in recent years. In this study, we investigated whether αβT-cell therapy causes changes in the host's immune cell profile, and if so, the effect of these changes on prognosis.

Methods: Peripheral blood mononuclear cells (PBMCs) from 30 gastric cancer patients who had completed one course of αβT-cell therapy were analyzed.

Identification of prognostic factors for γδT cell immunotherapy in patients with solid tumor.

Background Aims: Activated γδT cells have been shown to exhibit cytotoxicity against tumor cells. However, the efficacy of γδT cell immunotherapy for a large number of patients with solid tumors remains unclear. In this study, we examined the efficacy of γδT cell immunotherapy using in vitro-activated γδT lymphocytes in combination with standard therapies in terms of the survival of patients with solid tumors, and determined prognostic factor for γδT cell immunotherapy.

Prognostic Factors for Colorectal Cancer Patients Treated With Combination of Immune-cell Therapy and First-line Chemotherapy: A Retrospective Study.

Background/aim: In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy using T lymphocytes activated in vitro with or without dendritic cells vaccination (DCs), in combination with 1st-line chemotherapies in terms of the survival of patients with advanced colorectal cancer (CRC).

Patients And Methods: A total of 198 patients who were diagnosed with advanced CRC and administered 1st-line chemotherapies were enrolled in this study. The correlation between overall survival (OS) and various clinical factors was examined by univariate and multivariate analyses.

Significant clinical response of advanced colorectal cancer to combination therapy involving capecitabine and adoptive cell transfer therapy: a case report.

Significant clinical response was obtained in a patient with stage IV colorectal cancer (CRC) following combination therapy involving capecitabine and adoptive cell transfer therapy. She had laparoscopic lower anterior resection and left liver metastatic carcinoma resecting in 20th, February, 2017. Capecitabine was used to further treatment for an unresectable hepatic metastasis.

Prognostic Factors for Pancreatic Cancer Patients Treated with Immune-cell Therapy.

Background/aim: The past 17 years, immune-cell therapy has been administered to 990 patients with advanced or recurrent pancreatic adenocarcinoma and 50 patients with curatively resected pancreatic adenocarcinoma.

Materials And Methods: The correlation between overall survival (OS) and various factors including sex, age, performance status (PS), distant metastasis, chemotherapy, radiotherapy, and type of immune-cell therapy were evaluated by univariate and multivariate analyses.

Results: The median OS of advanced or recurrent pancreatic cancer was 5.

Comprehensive immunotherapy combined with intratumoral injection of zoledronate-pulsed dendritic cells, intravenous adoptive activated T lymphocyte and gemcitabine in unresectable locally advanced pancreatic carcinoma: a phase I/II trial.

Dendritic cell (DC)-based vaccines prepared using various antigen loading methods have been studied for cancer immunotherapy. The provocation of immunity by the direct injection of DCs without using tumor-specific antigens into tumors after apoptosis-inducing chemotherapy is more applicable. We previously reported that zoledronate-pulsed DCs (Zol-DCs) may induce tumor-antigen-specific CD8+ T cells by activating Vγ9γδT cells.

Efficacy of Adoptive Immune-cell Therapy in Patients with Advanced Gastric Cancer: A Retrospective Study.

Background: Conventional therapy for advanced gastric cancer (GC) has limited survival benefits. In this retrospective study, we aimed to investigate the efficacy of immune-cell therapy, using in vitro-activated T-lymphocytes with and without dendritic cells (DCs), in combination with standard therapies in terms of the survival of patients with advanced GC.

Patients And Methods: A total of 242 patients who were diagnosed as having stage-IV GC were enrolled in this study to receive immune-cell therapy with or without standard therapies, such as chemotherapy, surgery, or radiation therapy.

Clinical Study on the Medical Value of Combination Therapy Involving Adoptive Immunotherapy and Chemotherapy for Stage IV Colorectal Cancer (COMVI Study).

Background: Adoptive immunotherapy for cancer has evolved through development of novel technologies for generating a large number of activated killer cells, such as αβ T-cells, γδ T-cells, and natural killer cells. There has been no prospective trial of combination therapy involving adoptive immunotherapy and first-line chemotherapy for stage IV colorectal cancer. The present pilot study aimed to evaluate the safety and feasibility of combination therapy involving adoptive immunotherapy and chemotherapy for stage IV colorectal cancer (COMVI study).

Systemic Intravenous Adoptive Transfer of Autologous Lymphokine-activated αβ T-Cells Improves Temozolomide-induced Lymphopenia in Patients with Glioma.

In this clinical study, we investigated the safety and clinical usefulness of systemic adoptive immunotherapy using autologous lymphokine-activated αβ T-cells (αβ T-cells), combined with standard therapies, in patients with malignant brain tumors. Twenty-three patients with different malignant brain tumors, consisting of 14 treated with temozolomide (TMZ group) and 9 treated without temozolomide (non-TMZ group), received systemic intravenous injections of αβ T-cells (mean=10.4 injections/patient for the TMZ group, and 4.

Immunological quality and performance of tumor vessel-targeting CAR-T cells prepared by mRNA-EP for clinical research.

We previously reported that tumor vessel-redirected T cells, which were genetically engineered with chimeric antigen receptor (CAR) specific for vascular endothelial growth factor receptor 2 (VEGFR2), demonstrated significant antitumor effects in various murine solid tumor models. In the present study, we prepared anti-VEGFR2 CAR-T cells by CAR-coding mRNA electroporation (mRNA-EP) and analyzed their immunological characteristics and functions for use in clinical research. The expression of anti-VEGFR2 CAR on murine and human T cells was detected with approximately 100% efficiency for a few days, after peaking 6-12 hours after mRNA-EP.

Adoptive Chemoimmunotherapy Using Activated αβ T Cells for Stage IV Colorectal Cancer.

Background/aim: Adoptive immunotherapy of cancer is evolving with the development of novel technologies that generate proliferation of large numbers of αβ and γδ T cells. We evaluated the safety and efficacy of the combination of adoptive immunotherapy using αβ T cells with chemotherapy for stage IV colorectal cancer (CRC).

Patients And Methods: Fifteen patients with advanced or recurrent CRC received XELOX + bevacizumab + ex vivo expanded αβ T lymphocytes as a first-line chemoimmunotherapy.

Immunohistochemical Analysis of WT1 Antigen Expression in Various Solid Cancer Cells.

For a peptide-pulsed dendritic cell (DC) vaccine to work effectively in cancer treatment, it is significant that the target protein is expressed in cancer cells. Wilms' tumor 1 (WT1) has been identified as a molecular target for immune cell therapy of cancer. We evaluated the protein expression levels of WT1 in various solid tumors, as well as mucin 1 (MUC1) or major histocompatibility complex (MHC) class l molecules.