Robert Jenq, MD, City of Hope, Duarte, California, discusses the role of the microbiome in CAR T-cell therapy outcomes, highlighting evidence linking antibiotic exposure to reduced response rates. Emerging strategies such as fecal microbiota transplant and targeted bacterial therapies aim to restore the microbiome and improve CAR T-cell efficacy.

Transcript: 

My name is Rob Jenq, I’m a professor in the department of hematology and hematopoietic cell transplant at City of Hope, and I also direct the microbiome program. We had a session that was about how the microbiome can impact CAR T-cell patient outcomes. 

We had 3 speakers, I was chairing the session and was also one of the speakers. Melody Smith from Stanford University and Howard Hang from Scripps also gave fantastic talks. 

Melody kicked off the session, she’s a hematologist who treats patients undergoing CAR T-cell therapy and other types of transplant and cellular therapies. She summarized the literature, including her paper, which was one of the very first to look at the microbiome and CAR T-cell outcomes. One of her key findings was that if patients had been treated with antibiotics prior to CAR T-cell therapy, they were unfortunately less likely to do as well. In particular, response rates to CAR T-cell therapy were lower.

I gave the next talk, and I had co-led a similar study that included patients from MD Anderson in Houston, Moffitt Cancer Center in Florida, and 3 centers in Germany. We found something similar—that patients who received antibiotics prior to CAR T-cell therapy seemed to be at risk for not responding as well. This type of study is tricky to interpret because it’s what we call a retrospective analysis, we’re going back into patient charts and looking for patterns. It’s a great way to generate hypotheses and ideas about what might be happening and how we might improve outcomes, but it’s not definitive, because there can be confounding factors. And indeed, there were confounders: patients who received antibiotics didn’t receive them randomly—they often had more aggressive lymphoma or were sicker overall so they may already have been at higher risk for poorer outcomes with CAR T-cell therapy. We also have access to mouse models, where we can do CAR T-cell experiments. In a more recent study, we showed that if mice are treated with antibiotics, they also don’t do as well with CAR T-cell therapy. That provides additional evidence that the association we see in patients may reflect a real biological effect.

One of the final points I discussed was ongoing clinical trials. While I was at MD Anderson, I worked with Jason Westin and Nirav Saini to establish a fecal microbiota transplant study. This study is looking at whether patients can do better with CAR T-cell therapy if we restore their microbiome using a fecal sample from another individual. Since moving to City of Hope about a year and a half ago to direct the microbiome program, I’ve been working with colleagues there on similar approaches. There is a study led by Karamjeet Sandhu, in collaboration with Alex Khoruts from the University of Minnesota, who is providing microbiome capsules designed to restore the microbiome in our CAR T-cell patients.

The third speaker, Howard Hang, was also fantastic. He is chair of immunology at Scripps and has been studying how bacteria can impact cancer therapies, including immunotherapy. He has focused on a bacterium called enterococcus. He’s worked out a pathway showing how certain species of enterococcus, which live in the gut, produce enzymes that break down their own cell walls. In doing so, they release fragments that can be recognized by the immune system and stimulate immune responses. In mouse models, he showed that introducing this bacterium alone can significantly boost responses to immunotherapy, especially in mice that had been pretreated with antibiotics.

So this raises an interesting forward-looking idea—that instead of using complex approaches like fecal transplant, we might one day use more targeted, single-bacteria therapies to restore immune responsiveness and potentially improve outcomes for CAR T-cell patients.

Source: 

Jenq R. CAR-T response rates - how to harness the microbiome for our patients? Presented at AACR Annual . April 17 - 22, 2026; San Diego, California. ADT06.