How mRNA Vaccine Eradicates Pancreatic Cancer

Messenger RNA (mRNA) vaccines may be the hottest thing in science now, as they helped turn the tide against COVID-19. But even before the pandemic began, Memorial Sloan Kettering Cancer Center researchers had already been working to use mRNA vaccine technology to treat cancerVinod Balachandran a physician-scientist affiliated with the David M. Rubenstein Center for Pancreatic Cancer Research and the Parker Institute for Cancer Immunotherapy, is leading the only clinical trial to test mRNA vaccines for pancreatic cancer. The key to these vaccines appears to be proteins in the pancreatic tumors, called neoantigens, which alert the immune system to keep the cancer at bay.

The vaccines are custom-made for every person. The hope is that the vaccine will stimulate the production of certain immune cells, called T cells, that recognize pancreatic cancer cells. This could reduce the risk of the cancer returning after the main tumor was removed by surgeryIn 8 of 16 patients studied, the vaccines activated T cells that recognize the patient’s own pancreatic cancers. These patients also showed delayed recurrence of their pancreatic cancers, suggesting the T cells activated by the vaccines may be having the desired effect to keep pancreatic cancers in check

There has been great interest in using immunotherapy for pancreatic cancer because nothing else has worked very well. We thought immunotherapy held promise because of research we began about seven years ago. A small subset of patients with pancreatic cancer manage to beat the odds and survive after their tumor is removed. We looked at the tumors taken from these select patients and saw that the tumors had an especially large number of immune cells in them, especially T cells. Something in the tumor cells seemed to be sending out a signal that alerted the T cells and drew them in.


Antibodies Are The New Cancer Weapon

Antibody-based imaging* of a particularly aggressive form of breast cancer is undergoing clinical trials worldwide, but the path from trial to application is being hampered by a major obstacle: safety. Concerns stem from inefficient tumor targeting, which can result in accumulation in the bone marrow, liver and kidneys of the radioactive material necessary for the imaging. Recent efforts have focused on nanoscale delivery vehicles with immune components, but these vehicles are often still too large (20 nanometers or larger) for renal clearance after imaging.

Ulrich Wiesner, the Spencer T. Olin Professor of Engineering in materials science and engineering, in collaboration with Dr. Michelle Bradbury of Memorial Sloan Kettering Cancer Center (MSKCC) and Weill Cornell Medicine, has proposed a novel approach using ultrasmall silica nanoparticles – better known as “Cornell dots” (or C dots) – invented in his lab more than a dozen years ago. Their team – including researchers at pharmaceutical company MedImmune – have equipped the C dots with antibody fragments. Because the resulting conjugates are smaller than 8 nanometers, these C dots allow for renal clearance while achieving the specificity needed for efficient tumor targeting.

They report their discovery in in Nature Communications. Feng Chen, senior research scientist at MSKCC, and Kai Ma, postdoctoral researcher in the Wiesner lab, are co-lead authors. Wiesner said this research creates “a whole new runway” to employ antibody fragments for a number of diseases, cancer in particular, and for diagnostics as well as drug delivery – when combined in a single entity also known as “theranostics.”

A rendering of the Cornell prime dot (left) with an attached antibody fragment (center) binding to a HER2 cancer cell receptor (right). The dot and antibody attachment combined are less than 8 nanometers in diameter, the limit for renal clearance.

This is the first time we’ve worked with these antibody fragments,” Wiesner said, “thereby harnessing the power of antibodies in the fight against cancer.”

Cancer imaging is an umbrella term that covers the many approaches used to research and diagnose cancer. Originally used to diagnose and stage the disease, cancer imaging is now also used to assist with surgery and radiotherapy, to look for early responses to cancer therapies and to identify patients who are not responding to treatment.