The rising global cancer burden underscores the urgent need for innovative and effective therapies. Molecular and cellular immunology advances have revolutionized cancer immunotherapy, transforming laboratory discoveries into clinical breakthroughs. The Second Bone Marrow Transplant and Cellular Therapy Congress, held in Abu Dhabi, United Arab Emirates (UAE), on October 26 ^th - 27 ^th , 2024, and sponsored by the Abu Dhabi Stem Cells Center (ADSCC), convened global experts to discuss cutting-edge developments in adoptive cell transfer (ACT); chimeric antigen receptor T-cell (CAR-T) therapy, tumor-infiltrating lymphocyte (TIL) engineering and T-cell receptor (TCR) innovations. Discussions covered key challenges such as tumor microenvironment (TME) resistance, antigen escape, manufacturing complexity, cost-effectiveness, and accessibility. Experts emphasized the crucial role of biomarker identification in optimizing patient selection and improving treatment efficacy. Additionally, emerging strategies were highlighted to enhance the durability and specificity of cellular therapies, including next-generation CAR-T designs, combination approaches, and novel gene-editing technologies. With over 2,300 participants from academia, research, and healthcare, the event fostered international collaborations and knowledge exchange. The ADSCC continues to play a pivotal role in integrating advanced cellular therapies into healthcare systems, contributing to the expansion of precision oncology in the UAE and beyond. This review analyzes the latest advances in immunotherapy, highlighting their clinical impact, challenges, and future directions in the evolving landscape of cancer treatment, as debated during the congress.

Although the "original antigenic sin" (OAS) effects have been predicted against new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), only a few pieces of evidence are available regarding its impact on the safety and effectiveness of coronavirus disease 2019 (COVID-19) vaccines. This article aims to provide an immunological explanation for the delayed side effects of a SARS-CoV-2 vaccine during an episode of natural infection. We reported a case of a 39-year-old male healthcare worker who complained about pruritus and discomfort around the injection site of an inactivated SARS-CoV-2 vaccine administrated 18, 17, and 13 months earlier. Those symptoms resembled the side effects previously experienced with one of the booster doses, and a sole erythematous papule was also documented. The patient was diagnosed with COVID-19 one or two days after noticing these local signs and symptoms, and high serum titers of immunoglobulin M (IgM) and immunoglobulin E (IgE) were found five weeks after the onset, along with SARS-CoV-2-specific immunoglobulin G (IgG) antibodies. Therefore, the OAS might be a plausible phenomenon to consider in individuals immunized with inactivated vaccines and exposed secondarily to a wild virus with antigenic variations.

Background/Objectives: The ongoing evolution of SARS-CoV-2 has highlighted the limitations of parenteral vaccines in preventing viral transmission, largely due to their failure to elicit robust mucosal immunity. Methods: Here, we evaluated an intranasal (IN) vaccine formulation consisting of recombinant receptor-binding domain (RBD) adsorbed onto human probiotic Bacillus subtilis DG101 spores. Results: In BALB/c mice, IN spore-RBD immunization induced strong systemic and mucosal humoral responses, including elevated specific IgG, IgM, and IgA levels in serum, bronchoalveolar lavage fluid (BALF), nasal-associated lymphoid tissue (NALT), and saliva. It further promoted mucosal B cell and T cell memory, along with a Th1/Tc1-skewed T cell response, characterized by increased IFN-γ-expressing CD4⁺ and CD8⁺ T cells in the lungs. Conclusions: All in all, these findings highlight the potential of intranasal vaccines adjuvanted with probiotic B. subtilis spores in inducing sterilizing immunity and limiting SARS-CoV-2 transmission.

Background: Racotumomab-alum is an anti-idiotype vaccine targeting the NeuGcGM3 tumor-associated ganglioside. Clinical trials in advanced cancer patients have demonstrated low toxicity, high immunogenicity and clinical benefit. The goal of this study was to identify circulating biomarkers of clinical outcome. Methods: Eighteen patients with stage IIIb/IV non-small-cell lung cancer (NSCLC) were injected with racotumomab-alum as switch maintenance therapy after first-line chemotherapy. Treatment was administered until severe performance status worsening or toxicity. The frequencies of innate and adaptive lymphocytes were assessed by flow cytometry. Circulating factors were measured using multi-analyte flow assay kits. Results: The median overall survival was 16.5 months. Twenty-seven percent of patients were classified as long-term survivors. Patients with lower baseline frequencies of CD4+Tregs and central memory (CM) CD8+T cells displayed longer survival rates. Furthermore, higher baseline frequencies of NKT cells and a high CD8+T/CD4+Treg ratio were associated with longer survival. Interestingly, patients with significantly lower levels of effector memory (EM) CD8+T cells survived longer. The levels of NKT cells and terminal effector memory (EMRA) CD8+T cells were higher in long-term survivors in comparison with short-term survivors in post-immune samples. As expected, the ratio of CD8+T/CD4+Tregs showed significantly higher values during treatment in patients with clinical benefits. Regarding serum factors, pro-tumorigenic cytokines significantly increased during treatment in poor survivors. Conclusions: In advanced NSCLC patients receiving racotumomab-alum vaccine, longer survival could be associated with a unique profile of circulating lymphocyte subsets at baseline and during treatment. Additionally, certain pro-tumor-related cytokines increased in short-term survivors. These results should be confirmed in larger randomized clinical trials. This clinical trial was registered in the Cuban Clinical Trials Register (RPCE00000279).

Aim: Currently, malignant diseases represent a health issue worldwide. Among these, lung cancer is of growing importance, due to its high incidence and mortality. Chemotherapy, one of the most frequently used treatments, has shown its ability to induce accelerated immunosenescence in classic and as well non-classic lymphocyte compartments, being less described in the latter. The immune restoration strategies have demonstrated their ability to reverse immunosenescence and exhaustion markers in conventional lymphocyte subpopulations after chemotherapy. However, the possible immunorestorative effect on non-classical lymphocytes has not been widely reported. The aim of this study was to evaluate the effect of chemotherapy and the administration of a thymic polypeptide factor on non-classical lymphocyte populations in patients with advanced lung cancer. Methods: Eighteen patients with advanced lung cancer, were evaluated at baseline before and after platinum-based chemotherapy (4–6 cycles). All patients could complete treatment with a thymic polypeptide factor [Biomodulina T (BT)] at the end of chemotherapy. Blood from patients was collected by venipuncture in heparinized tubes before and after chemotherapy and at the end of BT treatment to analyze the frequencies of non-classical immune subpopulations by flow cytometry. Results: Natural killer (NK), natural killer T cells (NKT), and double-positive T lymphocyte (DPT) proportions reached normal values in patients diagnosed with advanced lung cancer before receiving cytotoxic treatment. Chemotherapy did not induce modifications in the total percent of NK, NKT, and DPT populations in these patients. However, the administration of BT decreased DPTs and NK cells expressing the cluster of differentiation (CD)57 molecule, which is considered a marker of immunosenescence. Conclusions: These results suggest a lower influence of platinum-based chemotherapy on non-classical lymphocytes and the potential to generate a reconstitution of lymphocyte subpopulations in patients with advanced lung cancer by using the thymic factor BT, which reveals a new possibility for improving the response to cancer immunotherapies [Cuban Public Registry of Clinical Trial (RPCEC, https://rpcec.sld.cu/en/trials/RPCEC00000358-En) identifier: RPCEC00000358].

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of pancreatic β-cells and the subsequent loss of insulin production. The regeneration of pancreatic β-cells from induced pluripotent stem cells (iPSCs) represents a promising therapeutic approach for restoring β-cell function in T1DM patients. However, ensuring the safety, functionality, and genetic stability of iPSC-derived β-cells is crucial for their clinical application. To address this challenge, a comprehensive literature review was conducted using PubMed/MEDLINE, Web of Science, and Scopus databases to identify relevant studies published up to October 2025. It included an analysis of key regulatory documents from the U.S. Food and Drug Administration (FDA), the European Medicines Agency on Advanced Therapy Medicinal Products (EMA ATMP), and the International Organization for Standardization (ISO). This article proposes a comprehensive quality control (QC) strategy for differentiating iPSCs into pancreatic β-cells, emphasizing a tiered approach with multiple checkpoints throughout the process. The strategy integrates advanced molecular and functional assays to evaluate cell identity, viability, stability, and microbiological safety. The proposed QC framework allows for continuous monitoring, early detection of potential issues, and real-time adjustments to optimize the differentiation process. The flexibility of this approach ensures its adaptation to emerging scientific advancements and regulatory requirements. This integrated and adaptable QC strategy enhances the likelihood of success in generating functional β-cells, laying a solid foundation for the clinical application of iPSC-derived β-cell therapies and offering hope for effective, long-term treatments for T1DM.