-
Bone Marrow Transplantation Jan 2008Clinical trials have established that T cells have the ability to prevent and treat pathogens and tumors. This is perhaps best exemplified by engraftment of allogeneic T... (Review)
Review
Clinical trials have established that T cells have the ability to prevent and treat pathogens and tumors. This is perhaps best exemplified by engraftment of allogeneic T cells in the context of hematopoietic stem-cell transplantation (HSCT), which for over the last 50 years remains one of the best and most robust examples of cell-based therapies for the treatment of hematologic malignancies. Yet, the approach to infuse T cells for treatment of cancer, in general, and pediatric tumors, in particular, generally remains on the sidelines of cancer therapy. This review outlines the current state-of-the-art and provides a rationale for undertaking adoptive immunotherapy trials with emphasis on childhood malignancies.
Topics: Child; Humans; Immunotherapy, Adoptive; Neoplasms; T-Lymphocytes; Virus Diseases
PubMed: 18026145
DOI: 10.1038/sj.bmt.1705930 -
International Journal of Hematology Nov 2021Over the past few years, cellular immunotherapy has emerged as a novel treatment option for certain forms of hematologic malignancies with multiple CAR-T therapies now... (Review)
Review
Over the past few years, cellular immunotherapy has emerged as a novel treatment option for certain forms of hematologic malignancies with multiple CAR-T therapies now routinely administered in the clinic. The limitations of generating an autologous cell product and the challenges of toxicity with CAR-T cells underscore the need to develop novel cell therapy products that are universal, safe, and potent. Natural killer (NK) cells are part of the innate immune system with unique advantages, including the potential for off-the-shelf therapy. A recent first-in-human trial of CD19-CAR-NK infusion in patients with relapsed/refractory lymphoid malignancies proved safe with promising clinical activity. Building on these encouraging clinical responses, research is now actively exploring ways to further enhance CAR-NK cell potency by prolonging in vivo persistence and overcoming mechanisms of functional exhaustion. Besides these strategies to modulate CAR-NK cell intrinsic properties, there are increasing efforts to translate the successes seen in hematologic malignancies to the solid tumor space. This review will provide an overview on current trends and evolving concepts to genetically engineer the next generation of CAR-NK therapies. Emphasis will be placed on innovative multiplexed engineering approaches including CRISPR/Cas9 to overcome CAR-NK functional exhaustion and reprogram immune cell metabolism for enhanced potency.
Topics: Animals; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Disease Susceptibility; Gene Editing; Genetic Engineering; Genetic Therapy; Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Killer Cells, Natural; Receptors, Chimeric Antigen; Translational Research, Biomedical; Treatment Outcome
PubMed: 34453686
DOI: 10.1007/s12185-021-03209-4 -
Research Initiative, Treatment Action :... Jan 1999
Topics: HIV Infections; Humans; Immunotherapy, Adoptive; T-Lymphocytes, Cytotoxic
PubMed: 11366227
DOI: No ID Found -
Stem Cells and Development Jun 2019
Topics: Hematologic Neoplasms; Humans; Immunotherapy, Adoptive; Killer Cells, Natural
PubMed: 31081719
DOI: 10.1089/scd.2019.0081 -
Current Treatment Options in Oncology Oct 2018Despite aggressive surgery, radiation, and systemic chemotherapy, the prognosis for patients diagnosed with malignant brain tumors remains extremely poor, and standard... (Review)
Review
Despite aggressive surgery, radiation, and systemic chemotherapy, the prognosis for patients diagnosed with malignant brain tumors remains extremely poor, and standard treatments carry significant risks for long-term neurocognitive deficits. There is a clear and urgent need for the development of more effective treatments that will add minimal toxicity to standard therapies for invasive brain cancers. Cancer immunotherapy is a treatment modality that holds promise for the delivery of tumor-specific cytotoxicity, with the potential to eliminate brain tumor cells without harming the eloquent brain.
Topics: Brain Neoplasms; Cancer Vaccines; Glioma; Humans; Immunotherapy, Adoptive; Oncolytic Virotherapy
PubMed: 30311004
DOI: 10.1007/s11864-018-0576-3 -
Experimental Dermatology Mar 2023Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) for melanoma is an example of the most successful cancer immune therapy. It achieves a durable... (Review)
Review
Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TILs) for melanoma is an example of the most successful cancer immune therapy. It achieves a durable complete response about ~20% of patients, and they might be cured. However, the ratio of patients with durable benefits is not high, and its complicated procedure prevents its diffusion. Therefore, many efforts to enhance the effect and simplify the protocol of TIL therapy have been made so far, resulting in the establishment of a simple and effective current TIL therapy that has been propagated to other institutes and countries. Moreover, TIL therapy and translational research using clinical samples derived from durable responders elucidate the important element for developing more effective cancer immune therapies in the future. This review introduced the brief history, attempts for the improvement and important findings elucidated by translational research of ACT for melanoma.
Topics: Humans; Melanoma; Lymphocytes, Tumor-Infiltrating; Adoptive Transfer; Immunotherapy, Adoptive
PubMed: 36382355
DOI: 10.1111/exd.14707 -
Journal of Clinical Oncology : Official... Sep 2023Historically, the outcomes for individuals with triple-class refractory and penta-drug refractory multiple myeloma (MM) have been poor because of a dearth of effective... (Review)
Review
Historically, the outcomes for individuals with triple-class refractory and penta-drug refractory multiple myeloma (MM) have been poor because of a dearth of effective treatment options. However, the advent of chimeric antigen receptor (CAR) T-cell and T-cell redirecting bispecific antibody (BsAb) therapies has led to unprecedented response rates and durations of response in heavily relapsed/refractory (R/R) populations. Currently, two B-cell maturation antigen (BCMA)-directed CAR T-cell therapies (idecabtagene vicleucel and ciltacabtagene autoleucel) as well as one BCMA/CD3 BsAb (teclistamab) have been approved for late-line (greater than four previous lines) R/R MM in the United States. The purpose of this review is to analyze the recent data for these approved therapies as well as provide an overview of other related CAR T-cell and BsAb therapies under development, including non-BCMA-targeting agents. We review efficacy and safety considerations, with particular focus on cytokine release syndrome, neurotoxicity, and infection risk. The relative merits and limitations of each class of therapy are discussed, as well as the areas of unmet need with respect to optimal sequencing and supportive care measures. We examine the factors that challenge equitable access to these novel therapies across minoritized racial, ethnic, and socioeconomic populations. Although it is evident that CAR T-cell and BsAb therapies will transform treatment paradigms in MM for years to come, significant work remains to identify the optimal utilization of these novel therapies and ensure equitable access.
Topics: Humans; Multiple Myeloma; Receptors, Chimeric Antigen; T-Lymphocytes; Immunotherapy, Adoptive; Treatment Outcome; Antibodies, Bispecific
PubMed: 37471687
DOI: 10.1200/JCO.23.00512 -
Surgical Oncology Clinics of North... Jul 2019The use of immunotherapies for solid and hematologic malignancies has demonstrated durable antitumor effects. Use of checkpoint inhibitors allows for immunologic... (Review)
Review
The use of immunotherapies for solid and hematologic malignancies has demonstrated durable antitumor effects. Use of checkpoint inhibitors allows for immunologic reactivation of the adaptive immune system against tumor-specific neoantigens and effective rejection. Recent developments in adoptive transfer of T cells has shown effective immune rejection of solid malignancies and durable regression. Adoptive cell transfer involves extraction of in vivo T lymphocytes, selection for or introduction of tumor reactive cells, in vitro expansion, and delivery of the T-cell product back to the patient. This article discusses the different approaches, challenges, and further directions of adoptive T-cell transfer in solid malignancies.
Topics: Animals; Cell- and Tissue-Based Therapy; Humans; Immunotherapy, Adoptive; Neoplasms
PubMed: 31079800
DOI: 10.1016/j.soc.2019.02.012 -
Journal of Clinical Oncology : Official... Feb 2021
Topics: Animals; Hematologic Neoplasms; Humans; Immunotherapy; Immunotherapy, Adoptive
PubMed: 33434044
DOI: 10.1200/JCO.20.03106 -
Biology of Blood and Marrow... Mar 2019Adoptive immunotherapy has shown efficacy in patients with relapsed/refractory acute myelogenous leukemia (AML). We conducted a prospective evaluation of cord blood...
Adoptive immunotherapy has shown efficacy in patients with relapsed/refractory acute myelogenous leukemia (AML). We conducted a prospective evaluation of cord blood (CB)-based adoptive cell therapy following salvage chemotherapy in patients with AML or myelodysplastic syndrome (MDS) and describe the safety and early outcomes of this approach. To enhance the antileukemic effect, we selected CB units (CBUs) with a shared inherited paternal antigen (IPA) and/or noninherited maternal antigen (NIMA) match with the recipients. Furthermore, the CBUs had total nucleated cell (TNC) dose <2.5 × 10/kg and were at least 4/6 HLA-matched with the patients; a higher allele-level match was preferred. Heavily pretreated adult patients with AML/MDS were enrolled. CBU searches were performed for 50 patients. CBUs with shared IPA targets were identified for all, and CBUs with NIMA matches were found for 80%. Twenty-one patients underwent treatment (AML, primary induction failure, n = 8; refractory relapse, n = 10, including 7 recipients of previous allogeneic HSCT; blast crisis chronic myelogenous leukemia, n = 1; MDS, n = 2). Most received combination chemotherapy; those not fit for intensive treatment received a hypomethylating agent. Response was defined as <10% residual blasts in hypocellular bone marrow at approximately 2 weeks after treatment. Ten of the 19 evaluable patients responded, including 5 of the 7 recipients of previous transplant. Response was seen in 4 of 4 patients with full CBU-derived chimerism, 2 of 2 of those with partial, low-level chimerism and 4 of 12 of the recipients with no detectable CBU chimerism. The most common adverse events were infections (bacterial, n = 5; viral, n = 2; fungal, n = 5). Grade IV acute graft-versus-host disease (GVHD) developed in 2 patients with full CBU chimerism; 2 other patients had grade 1 skin GVHD. A total of 11 patients died, 7 from disease recurrence and 4 from infections (1 early death; the other 3 in remission at the time of death). Overall, 12 patients proceeded to allogeneic HSCT; of those, 7 had responded to treatment, 3 had not (and had received additional therapy), and 2 had persistent minimal residual disease. In conclusion, the use of CB as adoptive immunotherapy in combination with salvage chemotherapy for patients with refractory AML/MDS is feasible, can induce disease control, can serve as a bridge to allogeneic HSCT, and has an acceptable incidence of adverse events. Alloreactivity was enhanced through the selection of CBUs targeting a shared IPA and/or NIMA match with the patients. CBUs with lower cell doses, already available in the CB bank and unlikely to be adequate grafts for adult transplants, can be used for cell therapy within a short time frame.
Topics: Adolescent; Adult; Chimerism; Female; Fetal Blood; Graft vs Host Disease; Humans; Immunotherapy, Adoptive; Infections; Leukemia, Myeloid, Acute; Male; Middle Aged; Myelodysplastic Syndromes; Prospective Studies; Salvage Therapy; Treatment Outcome
PubMed: 30414955
DOI: 10.1016/j.bbmt.2018.11.002