GeneTex Launches Novel Recombinant RAS (G12D Mutant) Antibody [HL10]

GeneTex is proud to announce the release of a novel recombinant rabbit monoclonal RAS (G12D mutant) antibody [HL10] (GTX635362). This antibody is the first commercially available recombinant antibody that demonstrates exceptional specificity by paraffin-embedded immunohistochemistry for this key tumorigenic mutant protein on sequence-verified human pancreatic tumor samples (Figure 1A). In addition, it specifically detects the RAS G12D mutation by western blot (Figure 1B).

Figure 1. (A) GeneTex's recombinant rabbit RAS (G12D mutant) antibody [HL10] (GTX635362) is sensitive and specific for the RAS G12D mutation by IHC of a KRAS G12D mutant pancreatic tumor tissue section (top) compared to a wild-type KRAS section (bottom). (B) The antibody is sensitive and specific for the RAS G12D mutation by WB of extracts from wild-type and mutant KRAS-confirmed human pancreatic cell lines. GAPDH for the loading control was detected by GTX100118. Lane1: HPDE. Land2: HPNE. Land3: AsPC1 (KRAS G12D). Land4: BxPC3 (KRAS WT). Lane5: CFPAC1 (KRAS G12V). Lane6: HPAC (KRAS G12D). Lane7: HPAF-II (KRAS G12D). Lane8: MIA PaCa-2 (KRAS G12C). Lane9: PANC1 (KRAS G12D). Lane10: SU86.86 (KRAS G12D).

The human RAS proteins (i.e., KRAS, HRAS, and NRAS) have been recognized for decades as some of the most potent triggers of malignancies. The three proteins are almost identical at the sequence and structural levels. Their normal function is to drive cell proliferation, with tight regulation allowing the protein to be turned “on” and “off” through binding and enzymatic processing of GTP. However, mutations in any of these RAS proteins, particularly KRAS and NRAS in human cancers, can keep them locked in the “on” state and cause uncontrolled neoplastic growth. These mutations occur most often at residues G12, G13, and Q61. RAS proteins are notoriously difficult to develop drugs against for both biochemical and structural reasons, though recent work using advanced computer modeling and compound screening and design technologies is offering new hope. Nevertheless, ongoing basic and clinical research efforts are essential for any substantial progress to be realized at the bedside.

KRAS has the distinction of being a preeminent oncoprotein, as it is mutated in more than 85% of RAS-altered cancers. The G12D mutation is found in various neoplasms with particularly high morbidity and mortality, including colorectal and pancreatic malignancies. Research has indicated that each mutation in a RAS protein can impart its own nuances on the protein’s behavior, arguing that future research progress will depend on the availability of reagents that can reliably identify each mutation. As Alexander Ball, M.D., a senior scientist at GeneTex, comments, “Many cancer researchers have refocused on conquering RAS, and this recombinant rabbit RAS (G12D) antibody [HL10] is exactly the type of reagent to facilitate their efforts.” The release of GeneTex’s recombinant rabbit RAS (G12D mutant) antibody [HL10] marks the fully operational status of GeneTex’s state-of-the-art recombinant antibody manufacturing facility and the continued evolution of GeneTex as a major developer and supplier of quality, rigorously validated antibody reagents that deliver reproducible performance. This new facility and production platform will spearhead the development of novel antibodies to advance scientific discovery and accelerate targeted therapies for clinical applications.