RE:RE:RE:RE:RE:RE:RE:AstraZeneca's ADC disappoints - on severe adverse eventsBreast cancer heterogeneity determines cancer progression, treatment effects, and prognosis.
The heterogeneity of breast cancer is attributed to differences in the genomic, epigenomic, transcriptomic, and proteomic characteristics of the cancer cells. These factors affect tumor properties such as proliferation, apoptosis, metastasis, and therapeutic response. This heterogeneity is also observed in tumor tissues among different patients or different metastases (intertumor heterogeneity) and within the individual tumor from the same patient (intratumor heterogeneity)
Breast cancer heterogeneity increases the difficulty of early diagnosis, treatment selection, and prognosis prediction.
The TME plays a significant role in tumor growth and metastasis and has always been an important obstacle during tumor therapy. The TME has many heterogeneous cell populations, including fibroblasts, adipocytes, immune cells, epithelial cells, pericytes, and extracellular matrix components. Interactions between tumor cells and their microenvironment contribute to tumor heterogeneity, thus promoting tumor progression.
ONCYs pelareorep as demonstrated its ability to remodel and prime the TME in advance of CPI administration, leading to the ability to address tumor heterogeneity expressed in breast cancers, in particular hr-positive (her2- negative) breast cancer
https://ehoonline.biomedcentral.com/articles/10.1186/s40164-022-00363-1
As already posted, ADCs have issues regarding T-cell resistance and exhaustion.
ONCY has identified the importance of TILs as a biomarker, which is underscored by the developing ability to predict treatment response to ICI therapy (predictive/prognostic biomarkers) based on their density and location, which ONCY has demonstrated in their clinical trials. ONCY has also demonstrated that pelareorep is able to expand the level and diversity of T-cells in the TME.
The value of a change in TILs within the TME as a response to cancer immunotherapy has also been demonstrated with immune checkpoint inhibition where an increase in TILs after treatment is prognostic, correlating with an improved survival outcome. ONCY measured the value change of TILs through the use of immunoscores like those used in ONCY's Aware-1 clinical study.
As a result, ONCY is able to be synergistically combined with immune checkpoint inhibitors, and enhance the effectivenes of both therapies while overcoming T-cell resistance and T-cell exhaustion.
As I posted beforehand, ADCs bearing a chemotherapy payload when used in combination with ONCY's ability to remodel the TME and expand the Cel-Tils in the blood and TME, sets the stage for addition immune checkpoint inhibitors, with the result being and effective combination I/O therapy - which is why Matt referenced the Enhertu Dynasty6 clinical trial using the chemotherpay payload letrozole.