In a new experimental form of immunotherapy, Portland doctors used an infusion of 16bn reprogrammed T cells to target a woman's cancerous cells.
Her tumour shrank by 62% in 30 days, and now, six months later, has stabilised at a 72% reduction of the original size.
The treatment, carried out by a team at the Providence Cancer Institute (PCI), was published in The New England Journal of Medicine.
The patient, Kathy Wilkes, had contacted the PCI, having previously had pancreatic cancer. KGW8 News reports that the cancer was back and had metastasised into her lungs.
“It’s one of the deadliest forms of cancer,” said Dr Eric Tran of the Earle A Chiles Research Institute, a division of PCI. Wilkes had fought her cancer with every conventional treatment, including surgery, radiation and multiple rounds of chemotherapy.
“I did not want to continue doing chemo; it would not save my life,” Wilkes had said. “It might prolong it, but not the quality of life I would want, so I researched immunotherapy.”
She found a previously published 2016 case report that detailed how a person with advanced colon cancer had been helped by an experimental type of gene therapy targeting a cancer mutation called KRAS G12D.
NBC News reports that with that in mind, she contacted the author of the report, Tran. Tran was at the National Institutes of Health when he treated the colon cancer patient, but had since moved on to the PCI in Oregon. Wilkes found him and inquired about undergoing the same type of therapy.
It turned out that she had the same genetic mutation as the colon cancer patient, despite having different forms of cancer.
Providence oncologist Dr Rom Leidner joined Tran to develop a special single-patient trial to tackle Wilkes’ cancer case.
The approach is reminiscent of CAR-T therapy, a form of treatment developed at the University of Pennsylvania.
“This is potentially a one-and-done treatment,” said Leidner, a co-author of the report and co-director of the head and neck cancer therapy programme at the PCI, of the new adoptive cell therapy, which involved drawing Wilkes’ blood, then isolating her immune system’s T cells. Those cells were reprogrammed to target a specific mutation of her cancer cells.
The doctors multiplied the invigorated T cells and infused 16bn of them back into Wilkes.
Within 30 days, her tumour had shrunk 62%, and six months later, had stabilised at a 72% reduction of the original size.
“She’s now living now as if she’s cancer free,” Leidner added.
Although her tumour has not completely gone, doctors said the treatment was keeping it in check and helping Wilkes live without symptoms.
The new treatment was historic, said Tran. “Providence Cancer Institute is first in the world to target a mutation with this sort of therapy.”
Tran and Leidner plan to expand trials to treat 24 more patients over the next two to three years. They noted similar efforts have not always been successful, but Wilkes’ experience shows its possible for patients to live longer and continue to have purpose.
Another patient with pancreatic cancer who received the same treatment at the PCI did not survive. It's unclear why the treatment seems to have been successful in one person but failed in another.
“We are working hard on trying to answer that question,” Tran said. “If we understand the mechanism, that could help us develop better therapies.”
Study details
Neoantigen T-cell receptor gene therapy in pancreatic cancer
Rom Leidner, Nelson Sanjuan Silva, Huayu Huang, David Sprott, Chunhong Zheng, Yi-Ping Shih, Amy Leung, Roxanne Payne, Kim Sutcliffe, Julie Cramer, Steven A. Rosenberg, Bernard A. Fox, et al.
Published in The New England Journal of Medicine on 2 June 2022
Summary
A patient with progressive metastatic pancreatic cancer was treated with a single infusion of 16.2×109 autologous T cells that had been genetically engineered to clonally express two allogeneic HLA-C*08:02–restricted T-cell receptors (TCRs) targeting mutant KRAS G12D expressed by the tumors. The patient had regression of visceral metastases (overall partial response of 72% according to the Response Evaluation Criteria in Solid Tumors, version 1.1); the response was ongoing at 6 months. The engineered T cells constituted more than 2% of all the circulating peripheral-blood T cells 6 months after the cell transfer. In this patient, TCR gene therapy targeting the KRAS G12D driver mutation mediated the objective regression of metastatic pancreatic cancer.
NEJM article – Neoantigen T-cell receptor gene therapy in pancreatic cancer (Open access)
See more from MedicalBrief archives:
CAR-T cell therapy for leukaemia associated with less dangerous side effects
FDA approves CAR-T cell therapy for some large B-cell lymphomas
Decade-long leukaemia remissions with CAR T-cell therapy – Landmark study