RE:ONCY's pelareorep can provide a fine T-cell boost for ADCs
Challenges Faced by Antibody-Drug Conjugates
Potential cancer resistance to ADCs
Cancer cells can gradually develop mechanisms to resist ADCs, reducing their effectiveness over time. This resistance may arise from various factors, including altered target cell surface expression or gene mutation, resistance to the ADC payload, failure in internalisation processes, impaired lysosomal function, or activation of drug-efflux pumps. Strategies to counteract this resistance include developing ADCs with alternative linkers and payloads, employing combined therapies that target complementary pathways, and enhancing immune-mediated killing of tumour cells by integrating immune checkpoint inhibitors into ADC treatment regimens.
ADC facing tumour heterogeneity
Cancer cells may exhibit diverse antigen expression levels, potentially reducing the efficacy of ADCs. To address this limitation, strategies like multispecific and bispecific antibody-drug conjugates, which incorporate multiple targeting domains, or combining ADCs with other therapies can broaden the spectrum of targetable antigens and enhance tumour penetration.
Off-target toxicities risk for ADC
A significant challenge associated with ADCs is the risk of off-target toxicities, especially with those using cleavable linkers. This can result in haematotoxicity, hepatotoxicity, and gastrointestinal reactions. Cleavable linkers often undergo hydrolysis in the bloodstream at a notable rate, causing the payload to be released prematurely in the extra-tumoral compartments, leading to unintended cytotoxicity. One approach to mitigate this toxicity is to enhance the stability of ADCs. Highly loaded ADCs are often unstable in plasma and exhibit high rates of non-specific uptake in the liver. This challenge can be addressed by reducing the Drug to Antibody ratio (DAR) or modifying the linker to decrease ADC hydrophobicity and toxicity.
Expensive cost of antibody-drug conjugates
A significant barrier to the widespread adoption of ADCs as a viable therapeutic option is their elevated cost. This cost encompasses expenses related to development, manufacturing, and administration, thereby restricting accessibility, particularly in certain regions or healthcare systems.
Only time will tell if antibody-drug conjugates are the future of cancer treatment
Antibody-Drug Conjugates stand at the forefront of innovative biotherapeutic solutions, showcasing immense potential in cancer treatment by offering targeted therapy and enabling precise cell death. This sets ADCs apart from conventional chemotherapy, reducing collateral damage to healthy tissues and minimising adverse effects. ADCs provide hope for patients seeking alternatives to traditional chemotherapy.
https://www.gtp-bioways.com/infographics/unlocking-antibody-drug-conjugates-cancer-treatment/