Multiple attributes differentiate InCell-RT as an ideal treatment for locally-advanced cancers
Conventional radiotherapy (RT) and chemotherapy agents produce DNA damage that is often repaired by endogenous DNA repair mechanisms. This allows adaptive cancer cells to "escape" and proliferate, creating LACs that are resistant to further treatment with DNA-damaging agents. InCell-RT employs a radioactive nucleoside analogue (i.e., 125I-UDR) that is virtually identical to thymidine to physically incorporate intracellular radiation directly into replicating DNA. This produces DNA destruction that cannot be repaired and irreversibly leads to cell death. Independence from DNA repair and other resistance mechanisms allows InCell-RT to be highly effective, even in heavily pre-treated patients with LACs that are resistant to conventional RT, chemotherapy, and other DNA-damaging agents.
LACs are genetically diverse, consisting of multiple cancer cell subpopulations with the potential for variable responses to individual therapies. Genetic diversity develops in tumors as they become locally-advanced because cancer cells are unstable and rapidly accumulate mutations in their DNA. Unless the molecular target of a specific therapy is universally expressed in all LAC subpopulations, there will inevitably be non-responsive cancer cells ("genetic variants") that continue to proliferate, creating LACs that are increasingly resistant to further treatment with these agents. InCell-RT is cytotoxic to all genetic subpopulations because it targets the core process of DNA replication, giving InCell-RT the potential to produce higher tumor response rates, increased remission times, and prolonged survival.
Conventional cancer therapies are often associated with dose-limiting toxicities that restrict their full efficacy potential. InCell-RT requires integration during DNA replication to localize nanometer-scale radiation within range to destroy DNA. Thus, InCell-RT can kill individual cancer cells without damaging normal non-dividing cells. This makes InCell-RT an ideal treatment for LACs, which are a mixture of dividing cancer cells and mostly quiescent (i.e., non-dividing) healthy tissue. In addition, locally administered 125I-UDR is rapidly eliminated from the systemic circulation, minimizing the risk to normal proliferative tissues that are distant from the treatment site (e.g., bone marrow, gastrointestinal tract, and mucosa). Selectivity for dividing cells within the treatment field, combined with a low risk of systemic side effects, allows InCell-RT to deliver efficacy that is not constrained by dose-limiting toxicities. And since cumulative side effects are not expected, repeated InCell-RT treatments are possible if tumor recurrence does occur.
Most "targeted" therapies are directed against a particular enzyme or receptor that is only expressed in a certain tissue type or genetic profile (e.g., PARP inhibitors for BRCA-related ovarian cancer). As such, the markets for these therapies are limited and often require the development of predictive biomarker assays to define the appropriate patient subpopulations. In contrast, all cancer cells must undergo DNA replication to proliferate and survive − there is no other mechanism that can compensate for this process. InCell-RT exploits this "core" cellular process to target destructive intracellular radiation directly into the DNA of individual cancer cells. Thus, the universal cytotoxic mechanism of InCell-RT is independent of tissue type, genetic profile, and biomarker status, providing the opportunity for broad use in many types of cancer.
125I-UDR is nanometer-scale intracellular radiation therapy
125I-UDR targets intracellular radiation to the DNA of dividing cells
Intracellular radiation irreversibly destroys DNA and kills the cell
Catheter-based infusion systems locally deliver 125I-UDR to LACs