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

Albarrán, Víctor; San Román, María; Pozas, Javier; Chamorro, Jesús; Rosero, Diana Isabel; Guerrero, Patricia; Calvo, Juan Carlos; González, Carlos; García de Quevedo, Coral; Pérez de Aguado, Patricia; Moreno, Jaime; Cortés, Alfonso; Soria, Ainara

doi:10.3389/fimmu.2024.1352805

Cited by 12 publications

References 118 publications

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Combining iRGD with HuFOLactis enhances antitumor potency by facilitating immune cell infiltration and activation

Shao,

Xin,

Qian

et al. 2024

Human Vaccines & Immunotherapeutics

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Multiple research studies have demonstrated the efficacy of lactic acid bacteria in boosting both innate and adaptive immune responses. We have created a Lactococcus lactis variant that produces a modified combination protein with Fms-like tyrosine kinase 3 ligand and co-stimulator O × 40 ligand, known as HuFOLactis. The genetically modified variant was purposely created to activate T cells, NK cells, and DC cells in a laboratory setting. Furthermore, we explored the possibility of using the tumor-penetrating peptide iRGD to deliver HuFOLactis-activated immune cells to hard-to-reach tumor areas. Following brief stimulation with HuFOLactis, immune cell phenotypes and functions were assessed using flow cytometry. Confocal microscopy was employed to demonstrate the infiltrative and cytotoxic capabilities of iRGD-modified HuFOLactis-activated immune cells within tumor spheroids. The efficacy of iRGD modified HuFOLactis-activated immune cells against tumors was assessed in xenograft mouse models. HuFOLactis treatment resulted in notable immune cell activation, demonstrated by elevated levels of CD25, CD69, and CD137. Additionally, these activated immune cells showed heightened cytokine production and enhanced cytotoxicity against MKN45 cell lines. Incorporation of the iRGD modification facilitated the infiltration of HuFOLactis-activated immune cells into multicellular spheroids (MCSs). Additionally, immune cells activated by HuFOLactis and modified with iRGD, in combination with anti-PD-1 treatment, effectively halted tumor growth and prolonged survival in a mouse model of gastric cancer.

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Combining iRGD with HuFOLactis enhances antitumor potency by facilitating immune cell infiltration and activation

Shao,

Xin,

Qian

et al. 2024

Human Vaccines & Immunotherapeutics

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Novel immunotherapeutic approaches in lung cancer: driving beyond programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte-associated Protein-4

Resuli,

Kauffmann-Guerrero

2024

Current Opinion in Oncology

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Purpose of review In this review, our aim is to highlight the latest novel immunotherapeutic approaches for advanced nonsmall cell lung cancer (NSCLC) beyond anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) and anti- cytotoxic T-lymphocyte-associated Protein-4 (CTLA4). Recent findings Immune checkpoint inhibitors (ICIs) revolutionized the treatment of advanced NSCLC. Despite that, patients develop primary or acquired resistance to ICIs. The discovery of novel approaches represents both an unmet need and an opportunity to improve outcomes in these patients. Summary We summarized the most relevant novel immune checkpoints, many of them in their early phase of testing, to provide a comprehensive overview of the state of the art of immunotherapy in NSCLC beyond PD-1/PD-L1 and CTL-4 inhibitors.

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Advances in cellular therapies for children and young adults with solid tumors

Choe,

Campbell,

Albert

2024

Current Opinion in Pediatrics

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Purpose of review Adoptive immunotherapy brings hope to children and young adults diagnosed with high-risk solid tumors. Cellular (cell) therapies such as chimeric antigen receptor (CAR) T cell, CAR natural killer (NK) cell, and T cell receptor (TCR) T cell therapy are potential avenues of targeted therapy with limited long-term toxicities. However, development of cell therapies for solid tumors is in its nascent stages. Here, we will review the current clinical experience, barriers to efficacy, and strategies to improve clinical response and patient access. Recent findings Cell therapies are shown to be generally safe and well tolerated. Strategies to optimize antitumor activity have now moved into early-phase trials. The immunosuppressive tumor microenvironment remains a major barrier to efficacy, and efforts are underway to gain better understanding. This will inform future treatment strategies to enhance the antitumor activity of cell therapies. Summary Clinical experiences to date provide important insights on how to leverage cell therapies against solid tumors. Key factors in advancing the field include a better understanding of immune cell biology, tumor cell behavior, and the tumor microenvironment. Lastly, improving access to novel cell therapies remains an important consideration in the conduct of clinical trials and for future implementation into standard practice.

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

Cited by 12 publications

References 118 publications

Combining iRGD with HuFOLactis enhances antitumor potency by facilitating immune cell infiltration and activation

Combining iRGD with HuFOLactis enhances antitumor potency by facilitating immune cell infiltration and activation

Novel immunotherapeutic approaches in lung cancer: driving beyond programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte-associated Protein-4

Advances in cellular therapies for children and young adults with solid tumors

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