Takis’ Post

Novel Immunotherapy Outperforms Standard CAR-T Treatment for Multiple Myeloma in Laboratory Trials #cancerimmunotherapy #cancerresearch #cartcells #stabtcells #multiplemyeloma #noveltherapies #immunooncology Exploring novel approaches in cellular therapy for multiple myeloma, researchers present STAb-T cells as a promising alternative to traditional CAR-T cells. Unlike conventional approaches, Díez-Alonso et al. introduce STAb-T cells, a novel solution showing remarkable efficacy. Instead of using traditional CAR-T cells, STAb-T cells release T cell-engaging antibodies targeting BCMA (a targt expressed by the cancer cells) and CD3. In both in vitro and in vivo comparisons, STAb-T cells outperform CAR-T cells, exhibiting superior target cell elimination and resistance to inhibition. This breakthrough in murine multiple myeloma models propels the development of BCMA-specific STAb-T cells, offering a promising therapeutic avenue for various hematological malignancies. https://lnkd.in/ejFBSDdV

Novel Immunotherapy Outperforms Standard CAR-T Treatment for Multiple Myeloma in Laboratory Trials #cancerimmunotherapy #cancerresearch #cartcells #stabtcells #multiplemyeloma #noveltherapies #immunooncology Exploring novel approaches in cellular therapy for multiple myeloma, researchers present STAb-T cells as a promising alternative to traditional CAR-T cells. Unlike conventional approaches, Díez-Alonso et al. introduce STAb-T cells, a novel solution showing remarkable efficacy. Instead of using traditional CAR-T cells, STAb-T cells release T cell-engaging antibodies targeting BCMA (a targt expressed by the cancer cells) and CD3. In both in vitro and in vivo comparisons, STAb-T cells outperform CAR-T cells, exhibiting superior target cell elimination and resistance to inhibition. This breakthrough in murine multiple myeloma models propels the development of BCMA-specific STAb-T cells, offering a promising therapeutic avenue for various hematological malignancies. https://lnkd.in/erRwre72

🔬 **New tool in Cancer Immunotherapy** 🔬 A recent publication by Li et al. presents a novel approach to tumor treatment by engineering a strain of *E. coli* to release the cytokine IFN-γ directly within the tumor core (SLIC–IFN-γ). This localized delivery method addresses the toxicity challenges of systemic therapies. Key findings: 1️⃣ **Promotes antitumor immunity** by polarizing tumor-associated myeloid cells and activating cytotoxic T cells. 2️⃣ **Overcomes PD-1 blockade resistance**, activating antigen-specific T cells and NK cells. These results suggest that SLIC–IFN-γ holds potential as a therapeutic strategy to address resistance to immunotherapy. #CancerResearch #Immunotherapy #Biotechnology #PrecisionMedicine #Oncology #PD1Blockade #SyntheticBiology #Microbiome #miraclesofscience https://lnkd.in/eSejGysZ

Very interesting....PPCR occurs in CAR T cell activation/ exhaustion too.

We highly recommend this exciting new article published in Cell regarding the discovery of a novel innate immune checkpoint IGSF8 and its application in cancer immunotherapy. The authors at GV20 Therapeutics found that IGSF8 expressed on tumors suppresses NK cell function by interacting with NK receptors. They further demonstrated that an antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells. Anti-IGSF8 alone or in combination with anti-PD1 indeed inhibits tumor growth in vivo. For more details, read the full article here: https://lnkd.in/e94c9VEh Cancer immunotherapy is one of the main topics of our society's 2024 Annual Conference which will take place in Cambridge, MA, USA, on Saturday, May 11, 2024. The co-founder and CEO of GV20 Therapeutics, Dr. Xiaole Shirley Liu was indeed an invited speaker of society's annual conference in 2022. Register for this year's conference via the following link if interested. https://lnkd.in/ecmFPA4v #antibodies #antibody #antibodytherapeutics #mabs #mab #antibodydiscovery #annualmeeting #annualconference #oncology #immunotherapy

2024 has been a year full of articles so far! 📃 Now you could read our group's latest article showcasing that "precision oncology is not a static but dynamic and reactive process" and "remarkable responses could be achieved after initial treatment failure", which is uncommon with conventional treatment strategies 👏 #PrecisionOncology #NewArticle

Extracellular vesicles (EVs) are the ‘small bubbles’ that our cells use to communicate with each other. They consist of a lipid coat and various signal molecules within—they can bind to other cells and then release their contents into the other cell. They’ve been of interest in cancer treatments for years…because they’d be able to cross barriers, and have reduced toxicity effects on the body. Researchers now have developed EVs that can bind to the fragment crystallizable (Fc) portions of antibodies—leaving the variable region of the antibody displayed for antigen recognition. Using mice models of breast cancer & melanoma, researchers developed Fc-EVs that targeted PD-L1 (a key target for immune checkpoint inhibition [ICI] immunotherapy treatments), and showed that this treatment reduced tumor growth & improved survival rate of mice compared to control treatments. While more research is needed—mainly to see if the treatment would have the same ‘success’ in humans…this is a key step towards almost personalized treatment plans for not only difficult to treat cancers, but also other diseases as well. #animalmodels #cancerresearch #extracellularvesicles #drugdelivery 

Hot off the press 🔥 Cancer-testis antigen burden (CTAB) is a novel immune biomarker that should be further explored. What is CTAB? Cancer-testis antigens are tumor antigens that are normally expressed in the testes but are ❌ aberrantly ❌ expressed in several cancers. The burden of CTAs or over expression of them has been shown to drive cancer metastasis. What was the study population? ⭐️ Patients with advanced NSCLC, treated with chemoimmunotherapy or immunotherapy alone, who underwent comprehensive genomic and immune profiling as standard of care. What were the results? 🔹Patients with high CTAB score and treated with immunotherapy revealed improved OS compared to those with low CTAB score 🔹There was significant co-expression of CTAB with TMB, however, not with PD-L1. 🚨The study suggests that CTAB score is a potential biomarker of immunotherapy response, and its expression appears to be independent from PD-L1 expression, an established biomarker of response to immunotherapy. Congratulations to R.J. Seager, Sarabjot Pabla, and our amazing team at Labcorp and OmniSeq 👏🏼 Rebecca Previs Eric Severson Kyle Strickland #immunooncology #immunotherapy #biomarker

#Ferroptosis is an intracellular iron-dependent form of cell death that is distinct from apoptosis, necrosis, and autophagy. Extensive studies suggest that ferroptosis plays a pivotal role in tumor suppression, thus providing new opportunities for cancer therapy. The development of resistance to cancer therapy remains a major challenge. A number of preclinical and clinical studies have focused on overcoming drug resistance. Intriguingly, ferroptosis has been correlated with cancer therapy resistance, and inducing ferroptosis has been demonstrated to reverse drug resistance. Herein, we provide a detailed description of the mechanisms of ferroptosis and the therapeutic role of regulating ferroptosis in reversing the resistance of cancer to common therapies, such as chemotherapy, targeted therapy and immunotherapy. We discuss the prospect and challenge of regulating ferroptosis as a therapeutic strategy for reversing cancer therapy resistance and expect that our review could provide some references for further studies.

Neoadjuvant #PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors:- •Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. •However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. •Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). •Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. •We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). •TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. •Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors. #highlights:- •The TME of HRD HGSOC is characterized by the enrichment of tumor-reactive T cells. •Neoadjuvant therapies preferentially suppress infiltrating eTregs in HRD tumors. •TME-wide interferon signaling correlates with HRD-dependent eTreg enrichment. •Joint targeting of PARP and eTregs in HRD tumors exhibits superior. therapeutic efficacy