Molecular Therapy, Journal Year: 2023, Volume and Issue: 32(1), P. 168 - 184
Published: Nov. 17, 2023
Language: Английский
Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)
Published: Feb. 21, 2023
Abstract Lung cancer is the primary cause of mortality in United States and around globe. Therapeutic options for lung treatment include surgery, radiation therapy, chemotherapy, targeted drug therapy. Medical management often associated with development resistance leading to relapse. Immunotherapy profoundly altering approach owing its tolerable safety profile, sustained therapeutic response due immunological memory generation, effectiveness across a broad patient population. Different tumor-specific vaccination strategies are gaining ground cancer. Recent advances adoptive cell therapy (CAR T, TCR, TIL), clinical trials on cancer, hurdles discussed this review. patients (without targetable oncogenic driver alteration) reveal significant responses when treated programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) checkpoint blockade immunotherapies. Accumulating evidence indicates that loss effective anti-tumor immunity tumor evolution. vaccines combined immune inhibitors (ICI) can achieve better effects. To end, present article encompasses detailed overview recent developments immunotherapeutic landscape targeting small (SCLC) non-small (NSCLC). Additionally, review also explores implication nanomedicine immunotherapy as well combinatorial application traditional along regimens. Finally, ongoing trials, obstacles, future outlook strategy highlighted boost further research field.
Language: Английский
Citations
526
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13
Published: Oct. 11, 2022
Immune checkpoint therapy via PD-1 antibodies has shown exciting clinical value and robust therapeutic potential in practice. It can significantly improve progression-free survival overall survival. Following surgery, radiotherapy, chemotherapy, targeted therapy, cancer treatment now entered the age of immunotherapy. Although immunotherapy remarkable efficacy, it also suffers from limitations such as irAEs, cytokine storm, low response rate, etc. In this review, we discuss basic classification, research progress, Besides, by combining resistance mechanism with analysis combination give our insights into development new anticancer strategies.
Language: Английский
Citations
149
Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)
Published: Feb. 7, 2023
Abstract In recent decades, immune checkpoint blockade and chimeric antigen receptor T cell (CAR-T) therapy are two milestone achievements in clinical immunotherapy. However, both show limited efficacies most solid neoplasms, which necessitates the exploration of new immunotherapeutic modalities. The failure CAR-T several neoplasms is attributed to multiple factors, including low antigenicity tumor cells, infiltration effector diverse mechanisms immunosuppression microenvironment. New adoptive therapies have been attempted for TCR-T, CAR-natural killer cells (CAR-NK), CAR-macrophages (CAR-M). Compared CAR-T, these certain advantages treating neoplasms. this review, we summarized 40-year evolution therapies, then focused on advances CAR-NK, CAR-M discussed their potential applications.
Language: Английский
Citations
71
Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(8), P. 523 - 539
Published: July 8, 2024
Language: Английский
Citations
48
Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14
Published: March 6, 2023
Adoptive cell therapy (ACT) has seen a steep rise of new therapeutic approaches in its immune-oncology pipeline over the last years. This is great part due to recent approvals chimeric antigen receptor (CAR)-T therapies and their remarkable efficacy certain soluble tumors. A big focus ACT lies on T cells how genetically modify them target kill tumor cells. Genetically modified that are currently utilized either equipped with an engineered CAR or (TCR) for this purpose. Both strategies have advantages limitations. While CAR-T already used clinic, these face challenges when it comes treatment solid New designs next-generation might be able overcome hurdles. Moreover, CARs restricted surface antigens. TCR-T targeting intracellular antigens provide necessary qualities In review, we will summarize major advancements technology. cover ongoing clinical trials, discuss current challenges, assessment future directions within field.
Language: Английский
Citations
47
Cancer Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 11
Published: May 24, 2024
Over the past two decades, immunotherapies have increasingly been considered as first-line treatments for most cancers. One such treatment is immune checkpoint blockade (ICB), which has demonstrated promising results against various solid tumors in clinical trials. Monoclonal antibodies (mAbs) are currently available inhibitors (ICIs). These ICIs target specific checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Clinical trial strongly support feasibility of this immunotherapeutic approach. However, a substantial proportion patients with cancer develop resistance or tolerance to treatment, owing tumor evasion mechanisms that counteract host response. Consequently, research focus aimed at identifying additional synergistic inhibitory receptors enhance effectiveness anti-PD-1, anti-programmed ligand (anti-PD-L1), anti-CTLA-4 treatments. Recently, several molecular targets identified, T immunoreceptor Ig ITIM domains (TIGIT), mucin domain containing-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), V-domain immunoglobulin suppressor (VISTA), B attenuator (BTLA), signal-regulatory α (SIRPα). Functional mAbs targeting these molecules under development. CTLA-4, PD-1/PD-L1, other recently discovered proteins distinct structures forefront research. This review discusses structures, well progress their potential applications.
Language: Английский
Citations
24
Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13
Published: Oct. 17, 2022
The overall efficacy of chimeric antigen receptor modified T cells (CARTs) remain limited in solid tumors despite intensive studies that aim at targeting multiple antigens, enhancing migration, reducing tonic signaling, and improving tumor microenvironment. On the other hand, how affinity engaging kinetics antigen-binding domain (ABD) affects CART’s has not been carefully investigated. In this article, we first analyzed 38 published CART trials correlated response rate to their ABD affinity. Not surprisingly, majority (25 trials) CARTs utilized high-affinity ABDs, but generated merely 5.7% rate. contrast, 35% patients treated with built from moderate-affinity ABDs had clinical responses. Thus, only have less off-target toxicity, also are more effective. We then reviewed effects on biology function CARTs, providing further evidence may be better development. end, propose a fast-on/fast-off (high K off ) CART-target engagement allow generate sufficient signaling kill without being driven exhaustion. believe studying CART-tumor interaction hold key designing effective for tumors.
Language: Английский
Citations
48
Diseases, Journal Year: 2022, Volume and Issue: 10(3), P. 60 - 60
Published: Sept. 6, 2022
Recent advances in cancer immunology have enabled the discovery of promising immunotherapies for various malignancies that shifted treatment paradigm. The innovative research and clinical advancements immunotherapy approaches prolonged survival patients with relapsed or refractory metastatic cancers. Since U.S. FDA approved first immune checkpoint inhibitor 2011, field has grown exponentially. Multiple therapeutic agents to manipulate different aspects system are currently development. These include vaccines, adoptive cell therapies (such as CAR-T NK therapy), monoclonal antibodies, cytokine therapies, oncolytic viruses, inhibitors targeting checkpoints demonstrated efficacy. immunotherapeutic been specific treatments, while others preclinical trial stages. Given success immunotherapy, there a tremendous thrust improve efficacy strategies implemented so far. Here, we present comprehensive overview development implementation being used treat cancer. We also highlight latest developments, emerging trends, limitations, future promises immunotherapy.
Language: Английский
Citations
46
Current Treatment Options in Oncology, Journal Year: 2023, Volume and Issue: 24(6), P. 628 - 643
Published: April 20, 2023
Opinion statement In approximately 15–20% of the patients diagnosed with breast cancer, it comprises triple negative (TN) subtype, which until recently lacked targets for specific treatments and is known its aggressive clinical behavior in metastatic disease. TNBC considered most immunogenic cancer subtype due to higher levels tumor infiltrating lymphocytes (TILs), mutational burden PD-L1 expression, providing a rationale immunotherapy. The addition pembrolizumab chemotherapy as first-line treatment resulted significantly improved PFS OS positive mTNBC, leading FDA approval. However, response rate ICB unselected low. Ongoing (pre)clinical trials aim further optimize efficacy widen application beyond tumors. Novel immunomodulatory approaches induce more inflamed microenvironment include dual checkpoint blockade, bispecific antibodies, immunocytokines, adoptive cell therapies, oncolytic viruses, vaccines. Preclinical data these novel strategies seems promising, but solid support mTNBC awaited. Biomarkers capturing degree immunogenicity such not limited TILs, CD8 T levels, IFNg signatures could deciding therapeutic strategy appropriate patient. Given 1) accumulating therapy options disease 2) heterogeneity from immune-desert tumors, challenge work towards subgroups enable personalized (immuno)therapy
Language: Английский
Citations
37
Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)
Published: Oct. 19, 2023
Abstract Immunotherapy has good potential to eradicate tumors in the long term. However, due low immunogenicity of tumor cells, current cancer immunotherapies are not effective. To address this limitation, we constructed a BSA-FA functionalized iron-containing metal-organic framework (TPL@TFBF) that triggers potent systemic anti-tumor immune response by inducing ferroptosis and pyroptosis cells releasing large quantities damage-associated molecular patterns (DAMPs) induce immunogenicity, showing excellent efficacy against melanoma lung metastases vivo. This nanoplatform forms through coordination between tannic acid (TA) Fe 3+ is then loaded with triptolide (TPL), which coated FA-modified BSA. The nanoparticles target FA modification, TPL, TA. reduced 2+ TA, triggering Fenton reaction resulting ROS production. Moreover, TPL increases production intracellular inhibiting expression nuclear factor erythroid-2 related (Nrf2). Such simultaneous amplification induces undergo pyroptosis, amounts DAMPs, stimulate antigen presentation dendritic (DCs) proliferation cytotoxic T lymphocytes (CD4+/CD8 + cells) inhibit metastasis. In addition, combining nanoparticle treatment checkpoint blockade (ICB) further inhibits growth. work provides new strategy for immunotherapy based on various combinations cell death mechanisms.
Language: Английский
Citations
34