Kanagamani K’s Post

This ADC review article looks so interesting to me.

𝐃𝐞𝐯𝐞𝐥𝐨𝐩𝐦𝐞𝐧𝐭𝐬 𝐢𝐧 𝐎𝐧𝐜𝐨𝐥𝐨𝐠𝐲: 𝐑𝐚𝐝𝐢𝐨𝐩𝐡𝐚𝐫𝐦𝐚𝐜𝐞𝐮𝐭𝐢𝐜𝐚𝐥𝐬 💡Radiopharmaceuticals are a blend of pharmaceuticals and radioactive materials that offer targeted therapy with precision, delivering therapeutic doses directly to cancer cells, while sparing healthy tissue. They contain a radioactive isotope, typically combined with a targeting molecule specific to cancer cells. 💡These radiopharmaceuticals are administered to patients, either orally or intravenously, and once inside the body, emit radiation, which can be in the form of gamma rays or beta particles, depending on the specific isotope used. 💡 The emitted radiation interacts with the cancer cells, damaging their DNA and causing cell death through various mechanisms, including apoptosis or direct cellular destruction. 💡 Radiopharmaceuticals may also indirectly affect nearby cancer cells through the bystander effect, where radiation-induced damage to neighboring cells contributes to overall tumor eradication. 💡The targeting molecule attached to the radiopharmaceutical enables it to bind specifically to receptors or antigens overexpressed on the surface of the cells, facilitating precise delivery of radiation to the tumor site. 💡 This approach minimizes systemic toxicity and reduces side effects compared to traditional radiation therapy, which may affect healthy tissues surrounding the tumor.

Researchers from the Karolinska Institutet have developed extracellular vesicles (EVs) that can bind the fragment crystallizable (Fc) portion of antibodies, so that the variable regions are displayed for antigen recognition. The Fc-binding EVs (Fc-EVs) can be decorated with different types of antibodies and thus be targeted to any tissue of interest. EVs are natural delivery vectors and mediators of biological signals, and here, the Fc-EVs technology is designed as a targeted cancer therapy using tumour-specific therapeutic antibodies to guide the EVs to tumour cells and to deliver antitumoural drugs. EVs with Fc-binding domains may be adapted to display other Fc-fused proteins, bispecific antibodies and antibody–drug conjugates. Read the full study at Nature: https://lnkd.in/eepjgtes #Biointron #Antibodies #DrugDevelopment #DrugDesign #Fc #Bispecific #ADC #Oncology #Technology #Therapeutics

Noxopharm Limited (ASX:NOX, OTC:NOXOF), an innovative #biotech company, has soared on new data regarding its CRO-67 preclinical drug for #PancreaticCancer that shows significantly reduced pancreatic tumours and barrier cells in a complex model. Pancreatic cancer is especially difficult to treat because tumours are surrounded by a dense barrier of cells that protects them from anti-cancer drugs, as well as from the body’s immune system. CRO-67 targets pancreatic cancer in a different and innovative way by acting as a novel dual-cell therapy, destroying both tumour and barrier cells. Investors reacted positively with shares as much as 48.81% higher in ASX trading this morning to A$0.125, a 2024 high. “We are very pleased with the outcome of these studies as they show that CRO-67 continues to have a dual-cell therapy effect in a variety of pancreatic cancer models, including this complex model where the bar is set much higher," Noxopharm CEO Dr Gisela Mautner said. “Pancreatic cancer has a very poor survival rate. There is clearly an unmet need to develop new treatments, either alone or in combination with existing treatments, to help alleviate patient suffering and help save many lives.” More at #Proactive #ProactiveInvestors #Biopharmaceutcials #Oncology #CellTherapy #NOX http://ow.ly/yqMP105FlYn

We highly recommend this new excellent ADC review paper published in Nature Reviews Clinical Oncology. The authors of this paper highlight advances in each ADC component (the monoclonal antibody, payload, linker and conjugation chemistry) and provide more-detailed discussions on selected examples of emerging novel ADCs of each format, enabled by engineering of one or more of these components. Several emerging ADC formats exist, including bispecific ADCs, conditionally active ADCs (also known as probody–drug conjugates), immune-stimulating ADCs, protein-degrader ADCs and dual-drug ADCs, and each offers unique capabilities for tackling these various challenges. Probody–drug conjugates are expected to have improved tumour specificity, whereas bispecific ADCs and dual-drug ADCs have the potential to combat drug resistance and tumour heterogeneity. Integrating immune-stimulating ADCs and protein-degrader ADCs with current treatment regimens might enable multimodal treatment, potentially through several distinct mechanisms of action. The first and corresponding author is Dr./Prof. Kyoji Tsuchikama at The University of Texas Health Science Center at Houston (UTHealth Houston). He was also an invited speaker of our Society’s 2021 mAbTalk Symposium with the theme of “New Horizon of Antibody Drug Conjugate (ADC)”. By the way, our society’s official journal, Antibody Therapeutics (2022 CiteScore: 6.4) calls for papers regarding “Antibody-Drug Conjugates for Cancer Treatment”. You are welcome to submit your ADC manuscripts to our journal. You may know more detailed information from the link below to the website of call for papers announcement. The deadline for submitting manuscripts for this ADC focused collection will be extended to August 31, 2024. https://lnkd.in/eU87q8zn   #antibodies #antibody #antibodytherapeutics #mabs #mab #antibodydiscovery #adc #adcs #antibodydrugconjugates

GenFleet Therapeutics announced China's National Medical Products Administration (NMPA) has approved the clinical trial application for GFH375 (VS-7375) in an open-label, multi-center phase I/II study targeting advanced solid tumor patients with KRAS G12D mutation. G12D mutation is the most prevalent KRAS mutation detected in human cancers, and no G12D-targeted therapies have been approved yet. GFH375 is a highly potent and selective KRAS G12D inhibitor targeting both "ON" (GTP-bound) and "OFF" (GDP-bound) states of the protein. According to the latest preclinical findings posted at 2024 AACR annual meeting, GFH375 demonstrated preliminary safety data, favorable oral bioavailability and potent efficacy across preclinical models; moreover, GFH375 holds the potential for treating G12D-mutant cancers with brain metastases. Please click the link for its full version: https://lnkd.in/gYS7mVHu Find out more at GenFleet's official website: http://www.genfleet.com/en #biotech #cancer therapeutics #immunology

The potential of targeting the same biological targets with both Antibody Drug Conjugates (ADCs) and Radioligand Therapy (RLT) is an area of active research. Nectin-4, a validated target in urothelial cancer with an approved ADC, was recently targeted with a novel PET agent (68Ga-N188 - a high affinity bicyclic peptide). However, the SUVmax values observed were low (1-4), an order of magnitude lower than those commonly seen with PSMA and Somatostatin PET imaging where successful RLT agents have been developed. This raises the question of whether RLT can be effectively applied to targets with low absolute uptake given the mechanism of action of RLT is entirely dependent on energy delivery. Michael Hofman's commentary in JNM (The Hierarchy of SUVs: From Diagnostics to Therapeutics and the Pathway to Effective Theranostics) discusses this issue. He highlights that the amount of energy delivered to tumor deposits is critical, which could be challenging with low uptake targets. Further research is needed to determine whether targets with low absolute expression can be effectively treated with RLT. It is possible that alpha labelled agents might unlock some of these overexpressed proteins more effectively, although caution is needed where there is expression in normal tissues as well. Recent safety data has started to highlight the profound cytotoxicity of alpha approaches. The heterogeneity of target expression presents another challenge given the short path length of alpha emissions, and the known "patchy" expression of most currently studied ADC targets.

A huge milestone for the field of cellular immunotherapy today as Iovance Biotherapeutics, Inc. has been granted accelerated approval by FDA for Amtagvi, an autologous tumor infiltrating lymphocyte (TIL) cell therapy indicated for adults with unresectable or metastatic melanoma resistant to at least 1 systemic prior therapy. Amtagvi is the first cellular therapy approved for a solid tumor indication (hopefully the first of many more to come). Among the 73 patients treated with Amtagvi at the recommended dose, the objective response rate was 31.5%, including three (4.1%) patients with a complete response and 20 (27.4%) patients with a partial response. Among patients who were responsive to the treatment, 56.5%, 47.8% and 43.5% continued to maintain responses without tumor progression or death at six, nine and 12 months, respectively. Amtagvi was granted several designations during its development, including orphan drug status, RMAT, fastrack and Priority Review. https://lnkd.in/geAz-Sjf #celltherapy #cellandgenetherapy #tils #immunotherapy #melanoma #celltherapymanufacturing #advancedtherapies #regenerativemedicine #regulatoryaffairs #cmc

Boundless Bio presents promising findings from their latest studies on BBI-355, a novel inhibitor of checkpoint kinase 1 (CHK1), at the AACR Annual Meeting 2024. The drug is being investigated as a potential treatment for oncogene amplified cancers, which are known for their resistance to chemotherapy and targeted therapies. Studies using preclinical tumor models have demonstrated that BBI-355 overcomes ecDNA-mediated targeted therapy resistance, exhibiting substantial antitumor activity in these models. Moreover, preliminary clinical pharmacodynamic data from the ongoing Phase 1/2 POTENTIATE clinical trial show that BBI-355 is well-tolerated and has the potential to inhibit CHK1 in both skin and tumor tissues. These findings support the continued development of BBI-355 as a differentiated treatment approach for oncogene amplified cancers. In addition, research presented at AACR suggests a potential role for ecDNA in acquired resistance to chemotherapy, expanding the potential applicability of ecDNA-directed strategies beyond its current focus on targeted therapy resistance. Boundless Bio remains encouraged by the preclinical and clinical data supporting the development of BBI-355. The ongoing Phase 1/2 POTENTIATE clinical trial will continue to evaluate the safety, efficacy, and tolerability of BBI-355 in patients with oncogene amplified cancers.

📃Scientific paper: Drug-resistant profiles of extracellular vesicles predict therapeutic response in TNBC patients receiving neoadjuvant chemotherapy Abstract: BACKGROUND: Predicting tumor responses to neoadjuvant chemotherapy (NAC) is critical for evaluating prognosis and designing treatment strategies for patients with breast cancer; however, there are no reliable biomarkers that can effectively assess tumor responses. Therefore, we aimed to evaluate the clinical feasibility of using extracellular vesicles (EVs) to predict tumor response after NAC. METHODS: Drug-resistant triple-negative breast cancer (TNBC) cell lines were successfully established, which developed specific morphologies and rapidly growing features. To detect resistance to chemotherapeutic drugs, EVs were isolated from cultured cells and plasma samples collected post-NAC from 36 patients with breast cancer. RESULTS: Among the differentially expressed gene profiles between parental and drug-resistant cell lines, drug efflux transporters such as MDR1, MRP1, and BCRP were highly expressed in resistant cell lines. Drug efflux transporters have been identified not only in cell lines but also in EVs released from parental cells using immunoaffinity-based EV isolation. The expression of drug resistance markers in EVs was relatively high in patients with residual disease compared to those with a pathological complete response. CONCLUSIONS: The optimal combination of drug-resistant EV markers was significantly efficient in predicting resistance to NAC with 81.82% sensitivity and 92.86% specificity. SUPPLEMENTARY INFORMATION: The online version contains supplement... Continued on ES/IODE ➡️ https://etcse.fr/ZAbL ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.