Lampgen Clinical Research’s Post

A great article featuring Carl June, the Father of CAR-T, was just published. It highlights his optimism for CAR-T therapies targeting Glioblastoma (our lead indication at KiraGen Bio) and reinforces his confidence in the future of ex vivo cell therapies. There's been much discussion lately about the emergence of in vivo therapies soon to enter the clinic, and how they'll coexist with ex vivo approaches. June, like us at KiraGen, believes both will play important roles for the foreseeable future. Ex vivo editing likely will always have some key advantages: -Larger payloads -No off-target cell toxicity concerns -Lower efficacy burden The technology for both approaches evolves in tandem. As in vivo editing improves, ex vivo products will likewise evolve to harbor more complex circuits and even higher multiplex edits. The result? Two distinct classes of cell therapies, each with its own pros and cons, providing oncologists with a diverse toolkit to combat cancer. At KiraGen, we're excited to be at the forefront of ex vivo innovation, pushing the boundaries of what's possible in cell therapy. Stay tuned for updates as we build upon such exciting recent clinical success for patients in need! (Credit for thoughts above: Jacob Kimmel and Dr. Shelby) https://lnkd.in/eKhEGr32

Our latest research article is now published online in Oncogene. We demonstrate how cancer-associated fibroblasts within the tumor microenvironment are selectively altering breast cancer signalling in response to the hormone Estrogen, paving their way to therapy resistance. We go further to highlight signalling pathways involved in this cross-talk by utilizing a functional drug screen. Thanks to all the other authors in making this a reality. https://lnkd.in/dbcjbjAm

This meta-analysis addresses a significant gap in the literature by comprehensively assessing the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non–small cell lung cancer (NSCLC) across both randomized and nonrandomized settings. With controversy existing regarding the efficacy of neoadjuvant chemoimmunotherapy for NSCLC patients with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%, this study aimed to compare neoadjuvant chemoimmunotherapy with chemotherapy based on adverse events, surgical, pathological, and efficacy outcomes. The analysis of 43 eligible trials comprising 5431 patients revealed that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across various endpoints, including overall survival, event-free survival, major and complete pathological response. Notably, patients with baseline tumor PD-L1 levels less than 1% showed a significant benefit in event-free survival with neoadjuvant chemoimmunotherapy. These findings highlight the potential of neoadjuvant chemoimmunotherapy as a promising treatment approach for resectable NSCLC, particularly for patients with lower PD-L1 expression levels. Source: JAMA oncology (Link to Article on comments) Mark Sorin Connor Prosty Kathy Nie Khaled Katergi Anikka S. Matthew Dankner, MD PhD Pierre Fiset Boris Sepesi Patrick Forde Mariano Provencio Jonathan Spicer Aline Atallah

Conclusions 1. Serial postoperative ctDNA assessment has strong prognostic value, provides a potential window for earlier therapeutic intervention, and may enable more effective monitoring than current clinical tests such as cancer antigen 15-3. 2. This study provides evidence that those with serially negative ctDNA tests have superior clinical outcomes, providing reassurance to patients with breast cancer. 3. For select cases with HR+ disease, decisions about treatment management might require serial monitoring despite the ctDNA-positive result. https://lnkd.in/dn_55Dp7

Highlighting the next Curebound 2023 Cure Prize winning team for their work on pancreatic cancer. This team from Salk Institute for Biological Studies and UC San Diego Health recently discovered that the predominant type of immune cell present in pancreatic cancers, the macrophage, can be changed from a tumor promoting cell to a tumor eliminating cell by inhibiting the function of a protein known as Syk. This project will determine if combining Fostamatinib, an FDA approved drug that blocks Syk function, with chemotherapy prior to surgery improves patient outcomes. “The outcomes for pancreatic cancer are the most unfavorable among all major malignancies in the United States. Our proposal to study the Syk inhibitor, fostamatinib, in combination with chemotherapy holds the potential to revolutionize the standard of care for pancreatic cancer. Curebound’s indispensable support is crucial for propelling foundational preclinical studies, arising from the collaborative efforts of basic scientists and physician-scientists, into the clinical trial stage.” Shweta Joshi, PhD UC San Diego Health Shweta Joshi, PhD (UCSD), Andrew Lowy, MD (UCSD), @Ronald Evans, PhD (Salk Institute), @Karen Messer, PhD (UCSD), Hitendra Patel, MBBS (UCSD) Read more about their research via curebound.org

➡️Glioblastoma is an aggressive form of brain cancer with limited effective treatment options and a low survival rate (12-18 months after diagnosis). ➡️Glioblastoma is heterogeneous, implying not all cells within the tumor have the same antigen and each person's glioblastoma is unique. ➡️This makes targeting a particular protein an ineffective therapeutic approach. The uniqueness of glioblastoma also means treatment that works for one patient might not be effective in another patient. ➡️This lead researchers at the University of Pennsylvania to develop a CAR T cell therapy that targets two proteins commonly found in brain tumors—EGFR and IL13Rα2. ➡️The therapy proved effective in reducing tumor size in all patients in an ongoing phase I clinical trial. ➡️The main draw back was the neurotoxicity observed in all patients, but it is manageable. ➡️A wider range of patients would help determine and improve it's efficacy and safety since glioblastoma is a unique tumor.

Excited to share our new paper focusing on Second Primary Malignancies (SPMs) following CAR T-cell therapy out today in Clinical Cancer Research! 👇 This first-in-kind meta-analysis spans 5,517 lymphoma and myeloma patients receiving a range of CAR-T products. Main Take-aways: - On metaregression modelling, we found that SPM occurrence after CAR-T is associated with (1) duration of follow up, (2) number of prior therapy lines, and (3) treatment setting (CT > RWS). - In a subgroup meta analysis of randomized Ph 3 clinical trials, we did not identify an increased frequency of SPMs with CAR-T relative to previous standard-of-care therapies. - T cell malignancies were exceedingly rare (point estimate of 0.09%) and not all of these were CAR + More research is needed to fully understand how CAR-T therapy shapes SPM risk on a patient individual level, but these results do not indicate that CAR-T is associated with increased SPM relative to other treatment options. Great work by lead-author Tobias Tix and fantastic to collaborate with investigators at Memorial Sloan Kettering Cancer Center LMU Klinikum München and Dana-Farber Cancer Institute including partner-in-crime Dr. med. David Cordas dos Santos ! https://lnkd.in/e3JA3A-b

Check out our new study! 

🔬 TBrachytherapy Boosts in High-Risk Prostate Cancer: A Comparative Review Key Findings: Effectiveness: Brachytherapy boosts enhance dose escalation, offering improved biochemical control and progression-free survival compared to EBRT alone. Clinical Evidence: Multiple randomized controlled trials, including the ASCENDE-RT study, demonstrate significant benefits of brachytherapy boosts, with over 50% improvement in biochemical failure rates when LDR is added. Advantages of HDR: HDR brachytherapy, due to its rapid dose delivery, may reduce acute toxicities and better suit the radiobiology of prostate cancer. This review underscores the importance of brachytherapy boosts in high-risk prostate cancer, despite decline in utilization. Careful consideration of the benefits and potential toxicities is essential in optimizing patient outcomes. Authors: Ben Fischer-Valuck, Hiram Gay, Sagar Patel, Brian C Baumann, Michalski Jeff https://lnkd.in/ec93JXHK #ProstateCancer #Brachytherapy #RadiationTherapy #MedicalResearch #CME #PhysicianInsights

In a recent article published on Cancer Network, Matthew Campbell highlighted significant advancements in therapeutic strategies for advanced renal cell carcinoma (RCC). Immunotherapy combinations, like nivolumab and ipilimumab, are now standard, with pembrolizumab showing promising results in the KEYNOTE-564 trial. Dr. Campbell expressed that in treatment decisions, molecular profiling and quality of life are key considerations with future hopes pinned on neoadjuvant therapies and biomarkers such as ctDNA. While progress has been made, Dr. Campbell believes we've only "begun to scratch the surface" in RCC therapy. https://lnkd.in/eeVCQBvV #RenalCellCarcinoma #Immunotherapy #CancerResearch #Oncology #MedicalAdvancements #ASCOGU2024 #CancerNetwork