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Last friday, August 2nd, the FDA announced the approval of a new treatment based on Gene and Cell Engineering. Indicated for adults with unresectable or metastatic synovial sarcoma, a rare form of cancer in which malignant cells develop and form a tumor in soft tissues of the body, this is the first immunotherapy approved by the FDA to use reengineered cells for the treatment of solid tumors. This new autologous immunotherapy is also the first FDA-approved treatment that uses T lymphocytes with a reengineered T cell receptor (TCR). The patient's own T cells are harvested, modified "outside the body" so that their TCR target the MAGE-A4 antigen expressed by cancer cells in synovial sarcoma, and then infused back into the patient/donor in a single intravenous administration. Similar to other immunotherapies, side effects associated with exacerbated immune responses and inflammation may occur, including Cytokine Release Syndrome (CRS) and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS). With the continued advancements of immunotherapies and the unquestionable connection between precise individual medicine and a functional immune system, I wonder: how much could be learned and the benefits of monitoring immune function and immune cells during one's lifetime and prior to disease onset? Read more here: https://lnkd.in/gvV2FAsD

🧬 CAR-T cell therapy is a ground-breaking and highly effective personalized treatment involving T cells from a patient’s immune system, which are genetically engineered to target and destroy cancer cells. While CAR-T cell therapy has shown remarkable clinical success in treating specific blood cancers, current manufacturing processes have significant room for improvement. 📃 Read the complete piece on Cell & Gene Therapy Insights, written by my colleagues Narjes Armanet and Felix Montero Julian 👇

Lung cancer - Tumor suppressor gene zygosity - A fundamental determinant of disease etiology and therapeutic sensitivity #lungcancer #tumorsuppressorgenes #zygosity #monoallelic #biallelic #targetedtherapy #VUS #MSK #MSKimpact

After more than a decade of waiting since the most recent FDA authorization in the indication, Adaptimmune has triumphantly crossed the finish line with FDA accelerated approval of TECELRA® (afamitresgene autoleucel, “afami-cel”) for adult patients with unresectable or metastatic synovial sarcoma. This innovative autologous engineered TCR T cell therapy targets the MAGE-A4 protein, prevalent in many cases of this rare, aggressive, and difficult-to-treat soft tissue solid tumor. CDx biomarker tests for HLA type and MAGE-A4 tumor expression will be required prior to treatment with TECELRA. The FDA’s nod follows compelling results from cohort 1 of the SPEARHEAD-1 trial, involving 44 patients with advanced unresectable or metastatic synovial sarcoma who had previously undergone at least one line of anthracycline or ifosfamide-containing chemotherapy. Patients received a single intravenous dose of afami-cel (transduced dose range 1·0 × 10^9–10·0 × 10^9 T cells) after lymphodepletion. The primary endpoint, overall response rate (ORR), was assessed by an independent review committee using RECIST v1.1 in the modified intention-to-treat population. The results? An ORR of 43%, with a median response duration of 6 months, and 39% of responsive patients maintaining their response for over a year. Having witnessed firsthand the damage that synovial sarcomas can provoke on their surrounding tissues in my past life as a histotech, I am overjoyed to see this FDA approval of a cell therapy product arrive at a time when solid tumor treatments have lagged significantly behind those for their liquid tumor counterparts. Progress! This achievement is a testament to the relentless dedication of patients, caregivers, healthcare providers, and countless indefatigable cell and gene therapy professionals who have collectively brought this therapy to fruition. It’s a banner day for the field of cell and gene therapy and I’m proud to be in it. #celltherapy #cellandgenetherapy #TCR #TCells #solidtumors #sarcoma #celltherapymanufacturing #CGT #biomarkers #CDx #regulatoryaffairs https://lnkd.in/gCyYa4rY

Because Waiting Shouldn't Be Part of Your Oncology Plan! We’re excited to launch OncoCore, our new DNA + RNA panel for cancer care at the upcoming #ASCO2024 Annual Meeting in Chicago. Designed to detect key gene changes quickly, OncoCore focuses on 32 important cancer-related genes and delivers results in just 3-4 days. This means faster, clearer insights to guide treatment decisions. Why OncoCore? ✅ Results within 3-4 days ✅ ≥99% Sensitivity & Specificity ✅ Covers targeted gene mutations for NSCLC, Melanoma, Cholangiocarcinoma, CRC, GIST, Thyroid, Urothelial & Bladder Carcinoma ✅ Immunotherapy Biomarkers: MSI, MMR, PD-L1 ✅ Highlights results in an easy-to-interpret report featuring mutations associated with FDA-approved treatments and clinical trial options.   Discover how OncoCore can make a difference in cancer care: https://lnkd.in/gD8BMueE

First, our pan-cancer epigenomic analysis revealed multiple primate-specific #ERV families that are enriched within tumor-specific accessible chromatin across all 21 solid tumor types profiled by TCGA. Second, our work shows that ERV-derived enhancers link oncogenic #AP1/MAPK signaling to pathological transcriptional rewiring in colorectal cancer. Components of the #MAPK pathway are frequently mutated in cancers, leading to oncogenic hyperactivation of MAPK signaling which promotes pathological gene expression and tumor cell proliferation. Last, we discovered that #LTR10 elements are frequently affected by tandem repeat expansions that could influence their regulatory activity. Although all LTR10 insertions are fixed in the human population, they contain internal tandem repeats that show high levels of length polymorphism associated with repeat instability, consistent with a recent report of variable-length SVA elements which also contain internal tandem repeats. #ScienceAdvances 17 Jul 2024 

CAR T therapies in multiple myeloma: unleashing the future The landscape of cancer treatment has evolved significantly with the emergence of CAR T-cell therapy, offering a groundbreaking approach in managing multiple myeloma. This innovative method, alongside traditional treatments like stem cell transplants and immunomodulatory medications, demonstrates promising results with its potent cytotoxic effects. The recent FDA approval of a second multiple myeloma CAR T-cell therapy signifies a new era in cancer care, highlighting its potential as a highly effective therapeutic option. Ongoing trials are exploring the capabilities of CAR T-cells in targeting specific antigens, bringing hope to patients with relapsed/refractory MM by enhancing treatment responses and reducing side effects. Understanding the history, functions, and limitations of CAR T-cells is crucial as we strive to develop innovative strategies that maximize their efficacy. This article provides valuable insights into the application of CAR T-cells in multiple myeloma treatment, emphasizing their potential and the strategies employed to overcome existing challenges. Join us in exploring the future of cancer care through CAR T therapies. #CancerTreatment #CAR-TTherapy #MultipleMyeloma #MedicalInnovations

🧬 CAR-T cell therapy is a ground-breaking and highly effective personalized treatment involving T cells from a patient’s immune system, which are genetically engineered to target and destroy cancer cells. While CAR-T cell therapy has shown remarkable clinical success in treating specific blood cancers, current manufacturing processes have significant room for improvement. 📃 Read the complete piece on Cell & Gene Therapy Insights, written by my colleagues Narjes Armanet and Felix Montero Julian 👇

The SOLTI-1402 CORALEEN phase II study revealed that neoadjuvant treatment with #letrozole and #ribociclib in high-risk early stage Luminal B breast cancer patients resulted in molecular downstaging, as evidenced by a substantial degree of intrinsic subtype conversion to Luminal A and a decrease in Ki67 immunohistochemistry expression. Both therapies resulted in a decrease in Ki67 and an increase in cell cycle arrest (CCCA); however, the mechanisms through which CCCA was achieved differed between the ribociclib and letrozole arm and the chemotherapy arm. Gene expression analysis indicated that the combination of ribociclib and letrozole did not demonstrate enrichment in cell populations with tumor-initiating properties, unlike traditional cytotoxic chemotherapy and letrozole monotherapy. The study found that changes in TIL (Tumor Infiltrating Lymphocytes) quantification may not be a reliable marker of response or as a comprehensive indicator of immune microenvironment change in the Luminal B population. Gene expression signatures associated with antigen-presenting cells showed increased expression in CCCA tumors post-chemotherapy, while the same modules displayed decreased expression after ribociclib and letrozole treatment. #cancerresearch #drugdiscovery #clinicalresearch https://lnkd.in/eH38xTsT

PoC of a new gene therapy idea to treat cancer. Asgard Thx's AT-108 reprograms tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells, induced tumor regressions, and established long-term systemic immunity in multiple mouse melanoma models. https://lnkd.in/di5gRNHK https://lnkd.in/dtFKphmd