“Our report demonstrates that we can successfully manufacture CAR T-cells in HIV-positive patients, and that CAR T-cells can produce durable remissions of HIV-associated diffuse large B-cell lymphoma,” Jeremy Abramson, MD, MMSc, lead study author, Massachusetts General Hospital, Boston, Massachusetts, told Cancer Therapy Advisor.
Looking at the other side of the equation — that is, “curing” HIV in a patient with cancer — was the focus of a proof-of-concept study recently published in the New England Journal of Medicine. The study described a man aged 27 years with HIV type 1 and acute lymphoblastic leukemia (ALL) who received a CRISPR-based therapy to treat both diseases.3
The treatment was an allogeneic stem cell transplantation, for which the transplanted stem cells were previously edited with gene-editing tool CRISPR-Cas9 to ablate CCR5. A mutation in the gene encoding for CCR5 is thought to be protective; CCR5 is the primary coreceptor that lets HIV enter and infect the cell, so without CCR5, the entry of HIV is blocked. (Recent evidence casts doubt on prior conclusions that found that mutations in the CCR5 gene also shorten lifespan.)4
However, while such a study on CRISPR would normally be considered a milestone for the field, a closer look at the details and methodology of the experiment suggests that protocols should be refined before other similar trials commence.
“It simply didn’t work,” said Daniel Dever, PhD, a research instructor in the department of pediatrics in the division of stem cell transplantation and regenerative medicine at Stanford University, California, during an interview with Cancer Therapy Advisor. Dr Dever is also affiliated with the laboratory of Matthew Porteus, a physician-scientist who has been involved in the quest to translate CRISPR-based lab research to therapies in the clinic.
The ALL remains in remission in 1 patient, but the patient’s HIV was not successfully eliminated, and as a result, the patient continues to take antiretroviral drugs to manage the infection.3
Perhaps even more problematic is the fact that some experts considered the study methodology to be so flawed that even the data that were collected about the safety of the approach were called into question — and the capture of this safety information was one of the main goals of the study. “The methods were rushed, unfortunately,” concluded Dr Dever, who was not involved in the study.