EGFR bi-armed autologous activated T cells

"Class I BRAF mts (V600) render aggressive biology to CRC and poor response to anti EGFR inhibitors... Class II and III BRAF mts are associated with improved outcomes with EGFR blockade and represent a distinct biological subgroup of pMMR CRC. Class III BRAF mts have lower MAPK activation, consistent with the pattern of kinase-dead mutations."

P1, N=15, Completed, Barbara Ann Karmanos Cancer Institute | Active, not recruiting --> Completed | N=30 --> 15

P1/2, N=2, Completed, Barbara Ann Karmanos Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Dec 2021 --> Jun 2021 | Trial primary completion date: Dec 2021 --> Jun 2021

The impetus for this study was the remarkable clinical response seen in our earlier phase I/II clinical trial: a pancreatic cancer patient with drug resistant tumors who showed progression of disease following three infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) was restarted on the initial low dose of 5-fluorouracil showed complete response, suggesting that BATs infusions may have sensitized patient's tumor for chemoresponsiveness. Gemcitabine or cisplatin-resistant cell lines show an increased proportion of CD44/CD24/EpCAM cancer stem like cells as well as an increased number of ABC transporter ABCG2 positive cells compared to the parental cell lines. These data suggest that bispecific antibody armed activated T cells can target and kill chemo-resistant tumor cells and also markedly augment subsequent chemotherapeutic responsiveness, possibly by modulating the expression of ABC transporters.

P1, N=30, Active, not recruiting, Barbara Ann Karmanos Cancer Institute | Trial completion date: Jun 2021 --> Dec 2021

P1/2, N=2, Active, not recruiting, Barbara Ann Karmanos Cancer Institute | Trial completion date: Dec 2020 --> Dec 2021 | Trial primary completion date: Dec 2020 --> Dec 2021