LIfT BioSciences has disclosed preclinical data demonstrating that its neutrophil alpha immunomodulatory product (IMAN) exhibits potent tumoroid killing of pancreatic cancer.
Tumoroids originate in patients with pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. The patient was unresponsive to conventional chemotherapy treatment with Abraxane (nab-paclitaxel), but initially responded positively to Gemzar (Gemcitabine), after which the tumor returned aggressively and stopped responding to any of the conventional chemotherapy.
For these patients, there are limited alternative options. Immune checkpoint inhibitors (ICI) may help a minority of patients, but ultimately, the chance of survival is less than 5%.
In the tumoroid model, similar results were observed with paclitaxel which had no cancer cell killing effect, whereas a single dose of gemcitabine resulted in tumoroid destruction. In comparison, a single dose of FAITH LIfT BioSciences resulted in strong tumoroid destruction.
Importantly, unlike paclitaxel and gemcitabine, which are fixed in their mechanism of action, and with gemcitabine’s initial effects often not lasting once the cancer adapts, the resulting IMAN prevents tumors from evading treatment by retaining recognition of tumor cells while they adapt (as exemplified by Hirschhorn and colleagues in last month’s Cell publication on how neutrophils eliminate tumor escapes).
IMAN therapy benefits in that it does not rely solely on antigen recognition in tumors such as, for example, T-cells. IMAN has multiple threat recognition and killing mechanisms, as well as the ability to recruit remnants of the immune system and assist other immuno-oncology therapies, including ICI, to attack solid tumors more effectively.
LIfT Biosciences is moving toward clinical trials
Alex Blyth, chief executive of LIfT BioSciences, said: “After patenting our N-LIfT technology platform in 2016 to produce FAITH with the hope of creating new ways to destroy solid tumors, we continue to see our neutrophil-based therapies work against their promises as we move into clinic. Positive pre-clinical results in pancreatic cancer demonstrate the potential of our IMAN as an alternative and second-line treatment option for patients who have not responded to currently available treatments.
“This is due to its unique ability to continuously kill cancer cells as they adapt and recruit the patient’s immune system to provide lasting immunity. We look forward to continuing to provide updates on LIfT Biosciences’ exciting research as we move toward clinical trials starting in the first half of next year.
IMAN has a unique dual action mechanism as a cell therapy, in that it both directly kills tumors and tunes the rest of the immune system to join in the attack. This new direct killing data builds on previously announced data by LIfT BioSciences using PDAC biopsies, showing that IMAN modifies the tumor microenvironment (TME) and then activates the patient’s own immune cells into attack mode, such as tumor infiltrating lymphocytes (TILs).
Data announced in the patient-derived pancreatic ductal adenocarcinoma organoid model builds on data released in September 2022, which demonstrated that N-LIfT cell therapy demonstrated tumor destruction across five different solid tumor types in the PDX tumoroid model, and data announced in March 2022 , which demonstrates that N-LIfT exhibits robust tumor cell killing in a tumoroid model of the lung with a significant advantage over current standards of treatment.
The current data builds on what the company said was a major breakthrough earlier this year, when it announced preclinical data showing that its immunomodulatory neutrophil alpha product has both cytotoxic and immunomodulatory functions.