Immunotherapy最新文献

Type 1 diabetes (T1D) is characterized by the autoimmune destruction of insulin-producing β-cells of the pancreatic islets necessitating lifelong insulin therapy. Despite significant advancements in diabetes technology with increasingly sophisticated methods of insulin delivery and glucose monitoring, people with T1D remain at risk of severe complications like hypoglycemia and diabetic ketoacidosis. There has long been an interest in altering the immune response in T1D to prevent or cure T1D across its various stages with limited efficacy. This review highlights immunomodulatory approaches over the years including the anti-CD3 monoclonal antibody teplizumab which is now approved to delay onset of T1DM and other interventions under current investigation.

The success of autologous chimeric antigen receptor (CAR)-T cells has changed the treatment landscape in relapsed and refractory multiple myeloma (MM) resulting in potential movement of CAR-T cells to the frontline treatment setting. However, one of the greatest weaknesses of this therapy is its autologous nature, which makes it time-consuming, labor intensive, and dependent on the patient's T cell fitness. The development of allogeneic CARs is critical to overcome these challenges and provide patients with an off-the-shelf alternative that is readily available. This review will investigate the current landscape and future perspectives of allogeneic CAR research in MM, exploring both pre-clinical research and active clinical trials. More specifically, it will focus on the advantages and disadvantages of various CAR cellular candidates including CAR-T, CAR-NK, and CAR-iNKT cells, among other more novel candidates.

Aim: We describe a single-center burden of admissions for irAE management and rechallenge feasibility.

Methods: A retrospective single-center study of patients receiving immunotherapy between 2015-2018 assessing irAE and immunotherapy rechallenge outcomes.

Results: 69 of 307 patients (22%) required 124 hospitalizations for irAEs. 8 required ICU admission (2.6%). 6 (1.9%) died from irAEs. Corticosteroids were used in 96% of admissions. Additional immunosuppression was required in 26 admissions (21%). 47 of 69 patients were rechallenged (68%). The median duration between toxicity and rechallenge was 49 days (range 17-994 days). 19 of 47 rechallenged patients (40%) were admitted for subsequent irAE. 19 patients of the rechallenged group (40%) were alive at last follow-up.

Conclusion: Immunotherapy rechallenge following prior irAE hospitalization is feasible but carries significant toxicity risk.

Aims: To demonstrate pharmacokinetic equivalence of CT‑P39 administered via auto-injector (CT‑P39 AI) and European Union-approved reference omalizumab via pre-filled syringe (EU-OMA PFS) in healthy Japanese adults.

Participants & methods: This open-label, Phase 1 study randomized participants (1:1) to a single 150 mg/mL dose of CT‑P39 AI or EU-OMA PFS. The primary endpoint was pharmacokinetic equivalence per area under the concentration-time curve from time zero to infinity (AUC_0-inf) and maximum serum concentration (C_max). Equivalence was concluded if the 90% confidence intervals (CIs) for the ratios of geometric least-squares means (gLSMs) were contained within the predefined 80-125% equivalence margin. Secondary endpoints comprised additional pharmacokinetics, pharmacodynamics, safety, and immunogenicity.

Results: Overall, 65 and 64 individuals were randomized to CT‑P39 AI and EU-OMA PFS, respectively. Pharmacokinetic equivalence between CT‑P39 AI and EU-OMA PFS was demonstrated for both AUC_0-inf (ratio of gLSMs [90% CI] 101.66 [95.31-108.45]) and C_max (93.91 [87.20-101.14]). Thirty-nine (60.0%; CT‑P39 AI) and 32 (50.8%; EU-OMA PFS) participants experienced treatment-emergent adverse events (TEAEs) with no serious TEAEs. Secondary endpoints were comparable between groups.

Conclusions: CT‑P39 AI was pharmacokinetically equivalent to EU-OMA PFS following a single dose in healthy Japanese individuals; pharmacodynamics, safety, and immunogenicity were comparable.

Light-based immunotherapy uses specific wavelengths of light to activate or modulate immune responses. It primarily employs two mechanisms: direct activation of immune cells and indirect modulation of the tumor microenvironment (TME). Several light-based technologies are under investigation or clinical use in immunotherapy, including photodynamic immunotherapy (PDIT) and photothermal therapy (PTT). Optogenetic tools have the potential to precisely control T-cell receptor activation, cytokine release, or the activity of other immune effector cells. Light-based technologies present innovative opportunities within the realm of immunotherapy. The ability to precisely regulate immune cell activation via optogenetics, alongside the improved targeting of cancer cells through photoimmunotherapy, signifies a transformative shift in our strategies for immune modulation. Although many of these technologies remain in the experimental stage for various applications, initial findings are encouraging, especially concerning cancer treatment and immune modulation. Continued research and clinical trials are essential to fully harness the capabilities of light technology in the context of immune cell therapy.

Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells both play essential roles in controlling viral infections by eliminating virus-infected cells. Unlike CTLs, which require priming and activation by antigen-presenting cells, NK cells possess a remarkable capacity to mount a rapid antiviral immune response immediately after infection. Additionally, they can bolster the adaptive immune system by secreting cytokines and directly interacting with other immune cells. However, during chronic human immunodeficiency virus (HIV) infection, various immune cells, including NK cells, experience functional impairments. This has led to the exploration of NK cell-based immunotherapy as a promising strategy to reverse these dysfunctions and contribute to the pursuit of a functional cure for HIV. Building on the success of NK cell therapies in cancer treatment, these approaches offer significant potential for transforming the HIV cure field. This review provides a comprehensive overview of the latest advances in NK cell-based immunotherapy for HIV, outlining the progress made and the key challenges that must be overcome to achieve a functional cure for people living with HIV.