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Adoptive-cell-transfer therapy for the treatment of patients with cancer.

ABSTRACT: Adoptive immunotherapy--the isolation of antigen-specific cells, their ex vivo expansion and activation, and subsequent autologous administration--is a promising approach to inducing antitumour immune responses. The molecular identification of tumour antigens and the ability to monitor the persistence and transport of transferred cells has provided new insights into the mechanisms of tumour immunotherapy. Recent studies have shown the effectiveness of cell-transfer therapies for the treatment of patients with selected metastatic cancers. These studies provide a blueprint for the wider application of adoptive-cell-transfer therapy, and emphasize the requirement for in vivo persistence of the cells for therapeutic efficacy.

SUBMITTER: Dudley ME

PROVIDER: S-EPMC2305722 | biostudies-literature | 2003 Sep

REPOSITORIES: biostudies-literature

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Adoptive-cell-transfer therapy for the treatment of patients with cancer.

Dudley Mark E ME Rosenberg Steven A SA

Nature reviews. Cancer 20030901 9

Adoptive immunotherapy--the isolation of antigen-specific cells, their ex vivo expansion and activation, and subsequent autologous administration--is a promising approach to inducing antitumour immune responses. The molecular identification of tumour antigens and the ability to monitor the persistence and transport of transferred cells has provided new insights into the mechanisms of tumour immunotherapy. Recent studies have shown the effectiveness of cell-transfer therapies for the treatment of ...[more]

PMID: 12951585

Similar Datasets

Adoptive cell therapy for cancer treatment.

Project description:Adoptive cell therapy (ACT) is a rapidly growing anti-cancer strategy that has shown promise in treating various cancer types. The concept of ACT involves activating patients' own immune cells ex vivo and then transferring them back to the patients to recognize and eliminate cancer cells. Currently, the commonly used ACT includes tumor-infiltrating lymphocytes (TILs), genetically engineered immune cells, and dendritic cells (DCs) vaccines. With the advancement of cell culture and genetic engineering techniques, ACT has been used in clinics to treat malignant hematological diseases and many new ACT-based regimens are in different stages of clinical trials. Here, representative ACT approaches are introduced and the opportunities and challenges for clinical translation of ACT are discussed.

| S-EPMC10624386 | biostudies-literature

Natural Killer Cell Adoptive Transfer Therapy: Exploiting the First Line of Defense Against Cancer.

Project description:Natural killer (NK) cells constitute an important component of the initial immunological response against transformed cells. However, chronic exposure to the tumor microenvironment can fundamentally alter the ability of NK cells to sufficiently control tumor progression. Thus, the adoptive transfer of healthy, functional NK cells as an interventional therapy has been an area of great interest for improving patient outcomes. Recent developments in the field have provided a better understanding of what makes the NK compartment effective against malignant cells. Moreover, there are now multiple potential sources of NK cell products for infusion as well as techniques to manipulate these cells to enhance their antitumor functions. This review explores the advantages and disadvantages of various sources of NK cells as well as prospective therapeutic enhancements to adoptively transferred NK cells.

| S-EPMC4763946 | biostudies-literature

Development of allogeneic NK cell adoptive transfer therapy in metastatic melanoma patients: in vitro preclinical optimization studies.

Project description:Natural killer (NK) cells have long been considered as potential agents for adoptive cell therapy for solid cancer patients. Until today most studies utilized autologous NK cells and yielded disappointing results. Here we analyze various modular strategies to employ allogeneic NK cells for adoptive cell transfer, including donor-recipient HLA-C mismatching, selective activation and induction of melanoma-recognizing lysis receptors, and co-administration of antibodies to elicit antibody-dependent cell cytotoxicity (ADCC). We show that NK cell activation and induction of the relevant lysis receptors, as well as co-administration of antibodies yield substantial anti-cancer effects, which are functionally superior to HLA-C mismatching. Combination of the various strategies yielded improved effects. In addition, we developed various clinically-compatible ex vivo expansion protocols that were optimized according to fold expansion, purity and expression of lysis receptors. The main advantages of employing allogeneic NK cells are accessibility, the ability to use a single donor for many patients, combination with various strategies associated with the mechanism of action, e.g. antibodies and specific activation, as well as donor selection according to HLA or CD16 genotypes. This study rationalizes a clinical trial that combines adoptive transfer of highly potent allogeneic NK cells and antibody therapy.

| S-EPMC3587427 | biostudies-literature

Adoptive cell transfer for patients with metastatic melanoma: the potential and promise of cancer immunotherapy.

Project description:BackgroundCurrent FDA-approved therapeutic options for patients with metastatic melanoma include dacarbazine, interleukin 2, ipilimumab, vemurafenib, dabrafenib, and trametinib, but long-term tumor regression using available agents remains out of reach for most patients. Adoptive cell transfer (ACT) with autologous tumor-infiltrating lymphocytes (TILs) has shown encouraging results in clinical trials, with evidence of durable ongoing complete responses in patients with advanced melanoma. Emerging techniques to engineer T-cell receptors (TCRs) or chimeric antigen receptors (CARs) using lymphocytes from peripheral blood may offer new tactics in ACT.MethodsWe reviewed the literature to provide a synopsis on the development and clinical trial results of ACT, as well as the future outlook for using ACT in patients with metastatic melanoma.ResultsACT with TILs as part of a lymphodepleting regimen has been shown in clinical trials to cause objective clinical responses in approximately 40% to 72% of patients with metastatic melanoma, with up to 40% of those patients experiencing complete responses lasting up to 7 years ongoing. Pilot trials using TCR-engineered cells against melanoma-associated antigens MART-1 and gp100 and the cancer-testis antigen NY-ESO-1 have shown clinical responses in patients with melanoma. CAR cells directed against melanoma have been tested only in preclinical models; however, CAR cells targeting other histologies such as lymphoma have elicited antitumor responses in patients.ConclusionsAn example of state-of-the-art personalized medicine, ACT is a potentially curative therapy for patients with metastatic melanoma. Ongoing trials aiming to simplify the regimens may allow a broader range of patients to be treated and enable ACT to be offered by academic cancer centers.

| S-EPMC6322197 | biostudies-literature

Trial Watch: Adoptive cell transfer immunotherapy.

Project description:During the last two decades, several approaches for the activation of the immune system against cancer have been developed. These include rather unselective maneuvers such as the systemic administration of immunostimulatory agents (e.g., interleukin-2) as well as targeted interventions, encompassing highly specific monoclonal antibodies, vaccines and cell-based therapies. Among the latter, adoptive cell transfer (ACT) involves the selection of autologous lymphocytes with antitumor activity, their expansion/activation ex vivo, and their reinfusion into the patient, often in the context of lymphodepleting regimens (to minimize endogenous immunosuppression). Such autologous cells can be isolated from tumor-infiltrating lymphocytes or generated by manipulating circulating lymphocytes for the expression of tumor-specific T-cell receptors. In addition, autologous lymphocytes can be genetically engineered to prolong their in vivo persistence, to boost antitumor responses and/or to minimize side effects. ACT has recently been shown to be associated with a consistent rate of durable regressions in melanoma and renal cell carcinoma patients and holds great promises in several other oncological settings. In this Trial Watch, we will briefly review the scientific rationale behind ACT and discuss the progress of recent clinical trials evaluating the safety and effectiveness of adoptive cell transfer as an anticancer therapy.

| S-EPMC3382856 | biostudies-literature

Pathogen-Boosted Adoptive Cell Transfer Therapy Induces Endogenous Antitumor Immunity through Antigen Spreading.

Project description:Loss of target antigens in tumor cells has become one of the major hurdles limiting the efficacy of adoptive cell therapy (ACT)-based immunotherapies. The optimal approach to overcome this challenge includes broadening the immune response from the initially targeted tumor-associated antigen (TAA) to other TAAs expressed in the tumor. To induce a more broadly targeted antitumor response, we utilized our previously developed Re-energized ACT (ReACT), which capitalizes on the synergistic effect of pathogen-based immunotherapy and ACT. In this study, we showed that ReACT induced a sufficient endogenous CD8+ T-cell response beyond the initial target to prevent the outgrowth of antigen loss variants in a B16-F10 melanoma model. Sequentially, selective depletion experiments revealed that Batf3-driven cDC1s were essential for the activation of endogenous tumor-specific CD8+ T cells. In ReACT-treated mice that eradicated tumors, we observed that endogenous CD8+ T cells differentiated into memory cells and facilitated the rejection of local and distal tumor rechallenge. By targeting one TAA with ReACT, we provided broader TAA coverage to counter antigen escape and generate a durable memory response against local relapse and metastasis.See related Spotlight on p. 2.

| S-EPMC6946848 | biostudies-literature

In vivo imaging of T cell delivery to tumors after adoptive transfer therapy.

Project description:Adoptive transfer therapy of in vitro-expanded tumor-specific cytolytic T lymphocytes (CTLs) can mediate objective cancer regression in patients. Yet, technical limitations hamper precise monitoring of posttherapy T cell responses. Here we show in a mouse model that fused single photon emission computed tomography and x-ray computed tomography allows quantitative whole-body imaging of (111)In-oxine-labeled CTLs at tumor sites. Assessment of CTL localization is rapid, noninvasive, three-dimensional, and can be repeated for longitudinal analyses. We compared the effects of lymphodepletion before adoptive transfer on CTL recruitment and report that combined treatment increased intratumoral delivery of CTLs and improved antitumor efficacy. Because (111)In-oxine is a Food and Drug Administration-approved clinical agent, and human SPECT-CT systems are available, this approach should be clinically translatable, insofar as it may assess the efficacy of immunization procedures in individual patients and lead to development of more effective therapies.

| S-EPMC1941490 | biostudies-literature

Adoptive T cell therapy for the treatment of viral infections.

Project description: Not available

| S-EPMC4630547 | biostudies-literature

Adoptive Cell Transfer: Is it a Promising Immunotherapy for Colorectal Cancer?

Project description:The last decade has witnessed significant advances in the adoptive cell transfer (ACT) technique, which has been appreciated as one of the most promising treatments for patients with cancer. Utilization of ACT can enhance the function of the immune system or improve the specificity and persistence of transferred cells. Various immune cells including T lymphocytes, natural killer cells, dendritic cells, and even stem cells can be used in the ACT despite their different functional mechanisms. Colorectal cancer (CRC) is among the most common malignancies and causes millions of deaths worldwide every year. In this review, we discuss the status and perspective of the ACT in the treatment of CRC.

| S-EPMC6276301 | biostudies-literature

Safe engineering of CAR T cells for adoptive cell therapy of cancer using long-term episomal gene transfer.

Project description:Chimeric antigen receptor (CAR) T-cell therapy is a new successful treatment for refractory B-cell leukemia. Successful therapeutic outcome depends on long-term expression of CAR transgene in T cells, which is achieved by delivering transgene using integrating gamma retrovirus (RV) or lentivirus (LV). However, uncontrolled RV/LV integration in host cell genomes has the potential risk of causing insertional mutagenesis. Herein, we describe a novel episomal long-term cell engineering method using non-integrating lentiviral (NILV) vector containing a scaffold/matrix attachment region (S/MAR) element, for either expression of transgenes or silencing of target genes. The insertional events of this vector into the genome of host cells are below detection level. CD19 CAR T cells engineered with a NILV-S/MAR vector have similar levels of CAR expression as T cells engineered with an integrating LV vector, even after numerous rounds of cell division. NILV-S/MAR-engineered CD19 CAR T cells exhibited similar cytotoxic capacity upon CD19(+) target cell recognition as LV-engineered T cells and are as effective in controlling tumor growth in vivo We propose that NILV-S/MAR vectors are superior to current options as they enable long-term transgene expression without the risk of insertional mutagenesis and genotoxicity.

| S-EPMC4931286 | biostudies-literature

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