Tecelra (afamitresgene autoleucel) / Adaptimmune, US WorldMeds - LARVOL DELTA

A PHASE II STUDY OF HIGH DOSE IFOSFAMIDE IN METASTATIC/LOCALLY ADVANCED SYNOVIAL SARCOMA FROM A TERTIARY CARE CENTER IN INDIA (CTOS 2025) - "Others treatment options like Anlotinib and cellular therapies like afamitresgene autoleucel are either expensive or not suitable due to very low positivity of HLA-02 in Indian populationAs Indian and international data is lacking, we are doing this phase II study and analyse the effectiveness of this drug in this particular sarcoma type.Primary objective: • To study single agent ifosfamide in relapsed metastatic synovial sarcoma patients as determined by overall response rate (Complete response + Partial Response)Secondary objectives include overall survival, Toxity profiles, Quality of life analysis and median progression free survival Study design: Single arm, Phase II, Simon 2-stage clinical trial Study setting: The study will be conducted at Department of Medical Oncology, BRAIRCH, AIIMS, New Delhi... N/A"

Metastases • P2 data • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

THE PATTERN.ORG SARCOMA CONSORTIUM: BUILDING A MULTI-INSTITUTIONAL DATA RESOURCE FOR THE SARCOMA RESEARCH COMMUNITY (CTOS 2025) - "Molecularly focused research has led to breakthroughs, notably afami-cel in synovial sarcoma and nab-sirolimus in PEComa... This pilot sarcoma data consortium project combined efforts from RCRF, UNC and PICI. These data offer some preliminary insights into the cohort, but we seek additional partners to facilitate a multi-institutional consortium around sarcoma sample and data collection and sharing. We plan to bring additional institutions in as we expand this resource in the coming year."

Clinical • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTLA4 • PD-1

SINGLE-CELL RNA SEQUENCING OF AFAMITRESGENE AUTOLEUCEL INDICATES MECHANISMS OF PERSISTENCE AND ANTI-TUMOR ACTIVITY (CTOS 2025) - "We hypothesize that MP with T-cell subsets poised for sustained effector function and long-lived memory formation are capable of longer post-infusion persistence, sustaining higher afami-cel pharmacokinetic exposure, and will discuss the gene expression programs underlying these different cellular potentials."

IO biomarker • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD4 • MAGEA4

Preclinical Proof of Concept for Decentralized Manufacturing of a MAGE-A4/CD8alpha-Expressing Autologous T-Cell Therapy for Solid Tumors (ASH 2024) - P1, P2 | "We investigated suitability of a decentralized, rapid, and fresh cell manufacturing platform to produce T cells expressing the MAGE-A4 TCR and CD8α co-receptor compared with the established central manufacturing process for uza-cel. Importantly, the GDM platform could significantly reduce total vein-to-vein time for eligible patients from several weeks to ~1 week. The GDM system will be used to supply MAGE-A4/CD8α–expressing T cells for a proof-of-concept clinical trial to assess their safety and efficacy in patients with advanced head and neck cancer."

IO biomarker • Preclinical • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Urothelial Cancer • CD4 • IFNG • MAGEA4

Discovery and validation of DARKFOXTM, a novel alternative open reading frame of FOXM1 that is an attractive cancer antigen for peptide-HLA targeting immunotherapy (SITC 2025) - "Background Targeted immunotherapies are a highly promising treatment strategy for solid tumors, exemplified by the recent FDA approvals of tebentafusp and afamitresgene autoleucel, which target Class I peptide-HLA (pHLA) antigens...It is characterised by minimal presence in normal tissues, homogeneous intratumoral expression, and robust presentation by HLA on the surface of tumor cells. ENA101, an EnTiCE® bispecific T-cell engager targeting DARKFOX-A3, is currently in IND-enabling studies."

IO biomarker • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOXM1

Single-cell RNA sequencing of afamitresgene autoleucel indicates mechanisms of persistence and anti-tumor activity (SITC 2025) - P2 | "(Glasgow, UK) funded by Adaptimmune. The authors would like to thank the patients, their families, caregivers, and the teams involved in the SPEARHEAD-1 trial.Trial Registration SPEARHEAD-1 is registered at ClinicalTrials.gov with ID NCT04044768.Ethics Approval SPEARHEAD-1 was approved by local or independent institutional review boards or ethics committees at each participating site and all patients provided written informed consent."

IO biomarker • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD4 • MAGEA4

Discovery and validation of DARKFOXTM, a novel alternative open reading frame of FOXM1 that is an attractive cancer antigen for peptide-HLA targeting immunotherapy (SITC 2025) - "Background Targeted immunotherapies are a highly promising treatment strategy for solid tumors, exemplified by the recent FDA approvals of tebentafusp and afamitresgene autoleucel, which target Class I peptide-HLA (pHLA) antigens...It is characterised by minimal presence in normal tissues, homogeneous intratumoral expression, and robust presentation by HLA on the surface of tumor cells. ENA101, an EnTiCE® bispecific T-cell engager targeting DARKFOX-A3, is currently in IND-enabling studies."

IO biomarker • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOXM1

Current progress and latest therapeutic options in immuno-oncology (PubMed, Dtsch Med Wochenschr) - "For solid cancers, these comprise the antibody-drug-conjugate Mirvetuximab Soravtansine for platinum-resistant ovarian cancer, the monoclonal antibody Zolbetuximab for Claudin-18.2 positive gastric adenocarcinoma and the checkpoint inhibitor Tislelizumab for esophageal squamous cell carcinoma. For the treatment of relapsed or refractory hematologic B cell malignancies, the use of bispecific T cell engaging antibodies like the BCMA-CD3 targeting Teclistamab and CD20-CD3 targeting Glofitamab were approved by the EMA recently.Combinatorial approaches of conventional chemotherapy and checkpoint inhibitors for the treatment of cholangiocarcinoma, urothelial carcinoma and endometrial carcinoma received recent approval.A CD38 antibody-based bridging therapy for the treatment of newly diagnosed multiple myeloma and the Glofitamab-based approach in combination with Gemcitabine and Oxaliplatin for relapsed DLBCL are the latest additions for hematologic malignancies after promising..."

Journal • Review • Biliary Cancer • Cholangiocarcinoma • Diffuse Large B Cell Lymphoma • Endometrial Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Hematological Disorders • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Synovial Sarcoma • Urothelial Cancer • CLDN18

Advancing human leukocyte antigen-based cancer immunotherapy: from personalized to broad-spectrum strategies for genetically heterogeneous populations. (PubMed, Trends Cancer) - "Human leukocyte antigen (HLA)-based immunotherapeutics, such as tebentafusp-tebn and afamitresgene autoleucel, have expanded the treatment options for HLA-A*02-positive patients with rare solid tumors such as uveal melanoma, synovial sarcoma, and myxoid liposarcoma...Last, we emphasize the urgent need for further research to better understand HLA allotype heterogeneity and its influence on tumor immunopeptidome-driven immune responses. We anticipate that these strategies will accelerate the development and implementation of both personalized and broad-spectrum HLA-based immunotherapies, and will ultimately improve cancer treatment across genetically heterogeneous patient populations worldwide."

Heterogeneity • Journal • Review • Eye Cancer • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Uveal Melanoma • HLA-A

Future Directions and Priorities for Cellular Therapy in Sarcoma: A Report from the Strategic Advances in Sarcoma Science Cell Therapy Breakout. (PubMed, Cancers (Basel)) - "Sarcomas are promising targets for adoptive cell therapy (ACT), as shown by afami-cel's success in synovial sarcoma, but broader impact requires new target discovery, optimal cell selection, improved conditioning, combination treatments, deeper tumor microenvironment understanding, and predictive biomarkers to achieve more durable responses for more patients."

IO biomarker • Journal • Review • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • MAGEA4

Clinical Utility of the Companion Diagnostic and Clinical Trial MAGE-A4 Expression Assays in Identifying Adults With Advanced Synovial Sarcoma for Treatment With Afamitresgene Autoleucel (CAP 2025) - P2 | "Despite being slightly more selective than the CTA, the MAGE-A4 CDxA demonstrated similar clinical utility to the CTA in selecting patients with MAGE-A4–positive SyS who may be eligible for afami-cel. Efficacy Results for Patients With Synovial Sarcoma in SPEARHEAD-1 Based on MAGE-A4 CDxA/CTA Status All authors are shareholders of Adaptimmune. Wang discloses that Adaptimmune sponsored Agilent development of the MAGE-A4 IHC 1F9 PharmDx."

Clinical • Companion diagnostic • IO biomarker • IO Companion diagnostic • Metastases • Melanoma • Sarcoma • Solid Tumor • Synovial Sarcoma • MAGEA4

Adaptimmune Reports Q2 Financial Results and Provides Business Update (Adaptimmune Press Release) - "Q2 Tecelra sales of $11.1m with 16 patients invoiced represents >150% growth vs Q1 2025."

Sales • Soft Tissue Sarcoma • Spindle Cell Sarcoma • Synovial Sarcoma

Adoptive T-Cell Therapy in Sarcomas. (PubMed, Curr Oncol Rep) - "The FDA approval of afamitresgene autoleucel for advanced synovial sarcoma and the breakthrough designation of letetresgene autoleucel for myxoid/round cell liposarcoma signify a major turning point...Tumour infiltrating lymphocyte therapy, including lifileucel, is under investigation with checkpoint inhibitors or oncolytic agents to enhance efficacy and manage toxicity...Challenges include HLA restriction, tumour heterogeneity, and manufacturing complexity. Future strategies involving novel antigens, multi-targeting, and combinatorial regimens could broaden patient eligibility and improve therapeutic outcomes."

Journal • Review • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD276 • CTAG1B • FGFR4 • HER-2 • MAGEA4

Top advances of the year: Sarcoma. (PubMed, Cancer) - No abstract available

Journal • Oncology • Sarcoma • Solid Tumor

US WorldMeds Completes Acquisition of Adaptimmune's Cell-Therapy Portfolio; Ensures Continued Patient Access to Tecelra and Advances Development of lete-cel (PRNewswire) - "US WorldMeds (USWM) reported the successful closing of the previously announced acquisition of Adaptimmune Therapeutics plc's (Adaptimmune) cell–therapy assets-including TECELRA (afamitresgene autoleucel), lete–cel, afami–cel, and uza–cel. The acquisition was first announced on July 28, 2025 and has now been finalized. Under the terms of the Asset Purchase Agreement, USWM paid $55 million in cash at closing and will fund up to an additional $30 million in performance-based milestone payments tied to commercial and regulatory outcomes....Key Highlights: (i) Patient care continuity: TECELRA will remain available to patients without interruption, now under USWM's stewardship; (ii) Future development: USWM plans to bring lete–cel to the U.S. market, with potential regulatory approval anticipated in 2026, and will continue development of uza–cel in collaboration with Galapagos."

Commercial • FDA approval • Liposarcoma • Spindle Cell Sarcoma • Synovial Sarcoma

Adaptimmune Announces Entry into Definitive Agreement for Sale of TECELRA, lete-cel, afami-cel and uza-cel Cell Therapies to US WorldMeds (Adaptimmune Press Release) - "Adaptimmune Therapeutics plc...announced its entry into a definitive agreement for the sale of TECELRA, lete-cel, afami-cel, and uza-cel cell therapies to US WorldMeds. Consummation of the sale is expected to occur before the end of the week....Adaptimmune will retain rights to its preclinical assets including PRAME, CD70, and its allogeneic program; Adaptimmune will restructure to support the transition of these therapies to US WorldMeds and to maximize value from its remaining assets."

Commercial • Spindle Cell Sarcoma • Synovial Sarcoma

New frontier of gene therapy: Tecelra's promise for metastatic synovial sarcoma. (PubMed, J Pak Med Assoc) - No abstract available

Journal • Gene Therapies • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Development of Afami-Cel–Engineered Cell Therapy for Advanced Synovial Sarcoma (ASCO 2025) - No abstract available

Metastases • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

FDA Approval Summary: Afamitresgene Autoleucel for Adults With HLA-Restricted MAGE-A4 Positive Unresectable or Metastatic Synovial Sarcoma After Prior Chemotherapy. (PubMed, Clin Cancer Res) - "This represents the first FDA approval of a T-cell receptor gene therapy. It is also the first FDA approval specifically for SS, representing a new treatment modality for this rare population who lack effective therapies."

Clinical • FDA event • IO Companion diagnostic • Journal • Epstein-Barr Virus Infections • Gene Therapies • Hematological Disorders • Infectious Disease • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A • MAGEA4

Cellular therapies in sarcoma and other solid tumors. (PubMed, Curr Opin Oncol) - "Clinically, these therapies highlight the need for improved patient selection criteria, and optimized antigen targeting. Toxicity management must also be taken into account, as cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) can be severe. Further studies should focus on improving safety and T cell persistence, and refining manufacturing processes to increase accessibility and scalability."

Journal • Brain Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Glioma • Hematological Disorders • Hematological Malignancies • Liposarcoma • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • CLDN18 • CTAG1B • PSCA

Adaptimmune Reports Q1 Financial Results and Provides Business Update (Adaptimmune Press Release) - "TECELRA launch 2025 YTD metrics: 28 ATCs available; 21 patients aphresed; and 14 doses invoiced; $4.0 million Tecelra net sales in Q1 2025....Initiate rolling BLA for lete-cel to treat synovial sarcoma and MRCLS in Q4 2025."

FDA filing • Launch • Sales • Liposarcoma • Sarcoma • Synovial Sarcoma

From lactation to tumor immune modulation: emerging roles of prolactin in regulating tumor antigen presentation in breast cancer (IMMUNOLOGY 2025) - "In an in vivo syngeneic mouse model with 4T1 TNBC cells, systemic knockdown of the prolactin receptor (LFPRLR) restored antigen presentation, increasing CD80 expression on dendritic cells and macrophages, reducing PD-L1, and activating CD4+ and CD8+ T cells. Our findings reveal a novel role for prolactin in inhibiting immune cell antigen presentation within the tumor microenvironment, suggesting that targeting PRLR signaling could enhance anti-tumor immunity.Keywords: Cells Dendritic Cells T Cells; Molecules Antigens/Peptides/Epitopes MHC; Processes Antigen Presentation/Processing"

IO biomarker • Breast Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8 • CD80 • PD-L1 • PRLR • TAP1

Review of Adoptive Cellular Therapies for the Treatment of Sarcoma. (PubMed, Cancers (Basel)) - "Engineered TCRs, particularly those targeting MAGE-A4 and NY-ESO-1, have shown promising clinical results in synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS), leading to the recent FDA approval of afamitresgene autoleucel (afami-cel) and letetresgene autoleucel (lete-cel)...Future research will focus on optimizing lymphodepleting regimens, mitigating toxicity, enhancing in vivo persistence, and combining ACT with other therapeutic agents. As clinical trials expand, ACT holds the potential to revolutionize sarcoma treatment by offering durable, targeted therapies for previously refractory disease."

Journal • Review • Hematological Malignancies • Liposarcoma • Melanoma • Multiple Myeloma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD276 • CTAG1B • HER-2 • MAGEA4

Development of MAGE-A4 IHC 1F9 pharmDx for melanoma-associated antigen 4 (MAGE-A4) detection in FFPE synovial sarcoma specimens for afamitresgene autoleucel therapy (AACR 2025) - "These studies demonstrated high analytical assay performance and observer scoring precision of the MAGE-A4 IHC 1F9 pharmDx assay in SyS and combined with sqNSCLC specimens at MAGE-A4 TIPS (≥ 2+) ≥ 75%."

Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • MAGEA4

Allele-specific HLA LOH frequencies and survival outcomes in cancer: a real-world analysis (AACR 2025) - "For instance, A*02:01-specific LOH was associated with worse survival in CRC (HR 0.5355, 95% CI 0.2991-0.9589), but showed a trend toward improved survival in LUAD (HR 1.342, 95% CI 0.7713-2.336), in all patients treated with any therapy.Our findings highlight that over 90% of cancer cases found in the database are genomically intact at the HLA class I locus, preserving the molecular complex needed for TCR-HLA:driver mutation-based therapies. However, the association of A*02:01-specific LOH with poorer survival in CRC and the opposite trend in LUAD underscores the need for further investigation into allele-specific factors that may influence outcomes across various cancer types, treatment lines, and therapeutic modalities."

Clinical • IO biomarker • Real-world • Real-world evidence • Colorectal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • TP53