From bench to bedside: the history and progress of CAR T cell therapy

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 15, 2023

Chimeric antigen receptor (CAR) T cell therapy represents a major breakthrough in cancer care since the approval of tisagenlecleucel by Food and Drug Administration 2017 for treatment pediatric young adult patients with relapsed or refractory acute lymphocytic leukemia. As April 2023, six CAR therapies have been approved, demonstrating unprecedented efficacy B-cell malignancies multiple myeloma. However, adverse events such as cytokine release syndrome immune effector cell-associated neurotoxicity pose significant challenges to therapy. The severity these correlates pretreatment tumor burden, where higher burden results more severe consequences. This observation is supported application CD19-targeted autoimmune diseases including systemic lupus erythematosus antisynthetase syndrome. These indicate that initiating early at low using debulking strategy prior infusion may reduce events. In addition, expensive has limited effectiveness against solid tumors. this article, we review critical steps led groundbreaking explore ongoing efforts overcome challenges. With promise effective safer development, are optimistic broader range will benefit from revolutionary foreseeable future.

Язык: Английский

---

Exploring treatment options in cancer: Tumor treatment strategies

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Июль 17, 2024

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical psychological challenges. Encouragingly, the landscape of tumor treatment has undergone a comprehensive remarkable transformation. Emerging fervently pursued modalities are small molecule targeted agents, antibody-drug conjugates (ADCs), cell-based therapies, gene therapy. These cutting-edge not only afford personalized precise targeting, but also provide enhanced comfort potential to impede disease progression. Nonetheless, it is acknowledged that these strategies still harbour untapped for further advancement. Gaining understanding merits limitations holds promise offering novel perspectives clinical practice foundational research endeavours. In this review, we discussed different modalities, including drugs, peptide antibody cell therapy, It will detailed explanation each method, addressing their status development, challenges, solutions. The aim assist clinicians researchers in gaining deeper diverse options, enabling them carry out effective advance more efficiently.

Язык: Английский

---

Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Июль 1, 2024

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements potential therapeutic applications, focusing primarily on two areas: emerging cell-based therapies promising non-cell modalities. Within context cell therapy, discuss capacity overcome existing translational challenges faced by mainstream therapy paradigms, provide a detailed discussion advantages principal design considerations for boosting efficacy as well list specific examples different disease scenarios. We then explore drug delivery, physical intervention therapies, other areas (e.g., bioadhesives, artificial tissues, biosensors), emphasizing utility beyond mere delivery vehicles. Additionally, complement our latest progress clinical application outline future research directions, particularly terms integration with advanced biomanufacturing This review aims present comprehensive view critical insights into selection both tailored meet requirements diverse diseases situations.

Язык: Английский

---

Development of NK cell-based cancer immunotherapies through receptor engineering

Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(4), С. 315 - 331

Опубликована: Март 5, 2024

Abstract Natural killer (NK) cell-based immunotherapies are attracting increasing interest in the field of cancer treatment. Early clinical trials have shown promising outcomes, alongside satisfactory product efficacy and safety. Recent developments greatly increased therapeutic potential NK cells by endowing them with enhanced recognition cytotoxic capacities. This review focuses on surface receptor engineering cell therapy discusses its impact, challenges, future directions. Most approaches based chimeric antigen receptors to allow target specific tumor antigens independent human leukocyte restriction. approach has precision potency NK-mediated elimination cells. In addition, T-cell also mediates intracellular epitopes, which broadens range peptides. Indirect peptide been improved optimizing immunoglobulin constant fragment expression signaling. Indeed, engineered an ability recognize destroy coated antibodies, thereby their antibody-dependent cellular cytotoxicity. The promote expansion, persistence, infiltration transferred microenvironment explored. Receptor-based strategies for sustained functionality within environment discussed, these providing perspectives counteract tumor-induced immunosuppression. Overall, led significant advances immunotherapies. As technical challenges addressed, innovative treatments will likely reshape immunotherapy.

Язык: Английский

---

Cancer cell-intrinsic mechanisms driving acquired immune tolerance

Immunity, Год журнала: 2023, Номер 56(10), С. 2270 - 2295

Опубликована: Окт. 1, 2023

Immune evasion is a hallmark of cancer, enabling tumors to survive contact with the host immune system and evade cycle recognition destruction. Here, we review current understanding cancer cell-intrinsic factors driving evasion. We focus on T cells as key effectors anti-cancer immunity argue that destruction by gaining control over pathways usually serve maintain physiological tolerance self. Using this framework, place recent mechanistic advances in into broad categories cell localization, antigen recognition, acquisition optimal effector function. discuss redundancy involved identify knowledge gaps must be overcome better target evasion, including need for better, routinely available tools incorporate growing mechanisms stratify patients therapy trials.

Язык: Английский

---

Intratumoral immune triads are required for immunotherapy-mediated elimination of solid tumors

Cancer Cell, Год журнала: 2024, Номер 42(7), С. 1202 - 1216.e8

Опубликована: Июнь 20, 2024

Язык: Английский

---

Immunosuppressive tumor microenvironment and immunotherapy of hepatocellular carcinoma: current status and prospectives

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Апрель 29, 2024

Abstract Hepatocellular carcinoma (HCC) is a major health concern worldwide, with limited therapeutic options and poor prognosis. In recent years, immunotherapies such as immune checkpoint inhibitors (ICIs) have made great progress in the systemic treatment of HCC. The combination treatments based on ICIs been trend this area. Recently, dual blockade durvalumab plus tremelimumab has also emerged an effective for advanced However, majority HCC patients obtain benefits. Understanding immunological rationale exploring novel ways to improve efficacy immunotherapy drawn much attention. review, we summarize latest area, ongoing clinical trials immune-based therapies, well strategies chimeric antigen receptor T cells, personalized neoantigen vaccines, oncolytic viruses, bispecific antibodies.

Язык: Английский

---

Current and future immunotherapeutic approaches in pancreatic cancer treatment

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Июнь 4, 2024

Abstract Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type tumor have remained grim long time. Currently, it extremely challenging to prevent or detect early enough effective treatment because patients rarely exhibit symptoms there are no reliable indicators detection. Most advanced spreading that difficult treat, treatments like chemotherapy radiotherapy can only slightly prolong their life by few months. Immunotherapy has revolutionized pancreatic cancer, yet its effectiveness limited tumor's immunosuppressive hard-to-reach microenvironment. First, article explains microenvironment highlights wide range immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered chimeric antigen [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced cells, immune checkpoint inhibitors, immunomodulators, vaccines, strategies targeting myeloid in context contemporary knowledge future trends. Lastly, discusses main challenges ahead immunotherapy.

Язык: Английский

---

CD8+ T cell-based cancer immunotherapy

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Апрель 29, 2024

Abstract The immune system in humans is a defense department against both exogenous and endogenous hazards, where CD8 + T cells play crucial role opposing pathological threats. Various immunotherapies based on have emerged recent decades, showing their promising results treating intractable diseases. However, the fight constantly changing evolving cancers, formation function of can be challenged by tumors that might train group accomplices to resist cell killing. As cancer therapy stepped into era immunotherapy, understanding physiological cells, studying machinery tumor escape, thereby formulating different therapeutic strategies become imperative missions for clinical translational researchers fulfill. After brief basics cell-based biology covered, this review delineates mechanisms escape discusses immunotherapy regimens with own advantages setbacks, embracing challenges perspectives near future.

Язык: Английский

---

Adoptive T cell therapy for solid tumors: current landscape and future challenges

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 14, 2024

Adoptive cell therapy (ACT) comprises different strategies to enhance the activity of T lymphocytes and other effector cells that orchestrate antitumor immune response, including chimeric antigen receptor (CAR) T-cell therapy, (TCR) gene-modified cells, with tumor-infiltrating (TILs). The outstanding results CAR-T in some hematologic malignancies have launched investigation ACT patients refractory solid malignancies. However, certain characteristics tumors, such as their antigenic heterogeneity immunosuppressive microenvironment, hamper efficacy antigen-targeted treatments. Other modalities, TIL emerged promising new strategies. has shown safety immunogenic cancers, mainly advanced melanoma, an exciting rationale for its combination checkpoint inhibitors. implementation clinical practice is hindered by several biological, logistic, economic challenges. In this review, we aim summarize current knowledge, available results, potential areas future research regarding use tumors

Язык: Английский

---