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Translational scientists aim to improve cellular therapies

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Vanderbilt-Ingram Cancer Center is committed to doing more than treating patients with the latest advancements in cellular therapies. Its physician-scientists are focused on expanding their use for more types of cancer and improving response rates among patients.

Andrew Jallouk, MD, PhD, assistant professor of Medicine, is a translational scientist committed to hastening the progression of laboratory discoveries into better treatments for cancer patients. After finishing an undergraduate degree in biomedical engineering and chemistry from Vanderbilt University, he then obtained a dual MD/PhD degree from Washington University in St. Louis followed by a clinical fellowship at MD Anderson Cancer Center in Houston, where he conducted clinical and laboratory research on the use of engineered cellular therapies for lymphoma. He was recruited to Vanderbilt-Ingram in 2023.

Q: Can you describe the role of a translational scientist in the medical realm?

A: Historically, there have been clinical investigators that run clinical trials, and there have been physician-scientists who work in the lab. That’s been great, but what this field needs are people who can speak both languages and really bring the two together. That’s what we are trying to do.

Q: What’s the next step for the advancement of cellular therapies?

A: With cellular therapies, we take the immune cells out of the patient, reprogram them and then put them back in. What’s really unique about this is the manufacturing step. If the treatment doesn’t work for some patients or is not working as well as we would like, we can figure out what’s going on there and then make tweaks during the manufacturing process to improve the therapies. What fascinates me about this technology is the bench-to-bedside (science lab progression to clinical use) and back to bench perspective. We’re putting these cellular therapies into patients, and we can see what’s happening — what is going well and what is not going well; what are the toxicities and how can we avoid these toxicities. We have a lot of ability to then feed that information back into the lab, optimize our manufacturing, optimize our patient selection and really try to make things better.

Q: What you’ve described is CAR-T therapy or chimeric antigen receptor T cell therapy. Isn’t that primarily for blood cancers?

A: There are no CAR-T cells approved for any solid tumors right now. There are other therapies called TIL therapies or TCR therapies. One of those, TIL, has just been approved for melanoma, and there’s a TCR therapy that’s been approved for synovial sarcoma. They all fall within the realm of immune therapies, where you’re using cells to fight cancer. The issue with that historically has been that solid tumors have a hostile tumor microenvironment, so it’s been hard to develop immunotherapies that overcome that.

Q: How much does your training as a biomedical engineer play into what you do?

A: I think it helps in terms of speaking both languages. I have a lot of great scientific training and give a lot of credit to my mentors, both in undergraduate and graduate school and throughout my training. The engineering background has really made it easy to pick up the concept of cellular engineering and the technologies that are associated with that. The PhD work that I did gave me a lot of experience and insight into various laboratory techniques, so it’s made it easier to keep doing what I’m doing on the laboratory end even when I have responsibilities on the clinical end as well.

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Children benefit in multiple ways from cellular therapy advancements

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Cancers that were once almost always fatal for children are now curable because of advancements in cellular therapies that Vanderbilt-Ingram Cancer Center pediatric oncologists and hematologists have introduced to Tennessee.

The advancements have included improvements for HLA (human leukocyte antigen) matching with stem cell donors, better medicines for infection prevention, new therapies for graft-versus-host disease (GVHD) and CAR-T therapies.

“We were one of the first sites in the state to be able to use CAR-T to treat our patients, and that’s really been a big game changer for some of our patients who had relapsed or refractory leukemia that would have otherwise been fatal,” said Carrie Kitko, MD, Ingram Professor of Pediatric Oncology and medical director of the Pediatric Stem Cell Transplantation Program.

The program has established itself as a leading innovator in preventing and treating GVHD, which occurs when donor immune cells begin attacking the stem cell recipient’s healthy tissue. Vanderbilt-Ingram is part of an international consortium called MAGIC that has developed risk-stratified treatments according to both GVHD symptoms at presentation and biomarkers, or certain proteins in their blood, to predict patients who are more or less likely to respond to treatments for GVHD.

“We have had several clinical trials to potentially improve outcomes for patients with GVHD. If you’re a low-risk patient, we’ve been able to offer trials where we avoid steroids, which are normally what we use to treat our GVHD patients, but steroids have lots of side effects that can be quite unpleasant,” Kitko said.

“You can identify those low-risk patients that don’t need steroids, and you can use a less toxic therapy. And then for the high-risk patients, if we know that they’re unlikely to respond to steroids, why wait for them to fail on steroids. We have been able to offer some of these studies to both pediatric as well as adult patients.”

Kitko is the senior author of a study published in 2024 in The New England Journal of Medicine that led to the Food and Drug Administration approving a new drug for recurrent or refractory chronic GVHD. Patients who were given the drug, axatilimab, had an overall response rate of 74%.

“Now, patients have access to more drugs to treat chronic GVHD, which is really a very morbid condition for many of our patients,” she said. “Moderate to severe chronic GVHD really impacts their quality of life and their ability to do normal day-to-day activities.”

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Vanderbilt-affiliated cellular therapy programs reaccredited

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The cellular therapy programs at Vanderbilt-Ingram Cancer Center, Monroe Carell Jr. Children’s Hospital at Vanderbilt, and the VA Tennessee Valley Healthcare System have received reaccreditation from the Foundation for the Accreditation of Cellular Therapy (FACT).

Founded in 1995, FACT establishes standards for high-quality medical and laboratory practice in cellular therapies. FACT is a nonprofit corporation co-founded by the International Society for Cell and Gene Therapy and the American Society for Transplantation and Cellular Therapy for the purposes of voluntary inspection and accreditation in the field of cellular therapy.

“FACT is an internationally recognized accrediting body for hospitals that offer stem cell transplant and cellular therapy, and recognition by FACT indicates that the accredited institution has met the most rigorous standard in every aspect of cellular therapy,” said Adetola Kassim, MBBS, MS, professor of Medicine and clinical director of the Adult Stem Cell Transplant Program. “This covers the entire spectrum of stem cell therapy from clinical care to donor management, cell collection, processing, storage, transplant, administration and cell release.”

The Vanderbilt and VA Tennessee Valley Healthcare System programs received accreditation notification April 14 after on-site inspections in October 2024. The accreditation is effective for three years.

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Scientific Symposium

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The Vanderbilt-Ingram Cancer Center 26th Annual Scientific Symposium, held April 22, focused on the theme “Artificial Intelligence in Cancer Research and Clinical Care.” The event also highlighted the achievements of trainees with a research poster competition and the announcements of graduate and undergraduate students of the year.

  • Jared Rhodes discusses the findings of his research with Alain Gobert, PhD.
  • Xiaopeng Sun, PhD, co-graduate student of the year, speaks about his research studying blood cell markers related to immunotherapy outcomes.
  • Pictured left to right are Christopher Willliams, MD, PhD, associate director for Research Education at Vanderbilt-Ingram, Michael Robinson, MD, Guochong “Damon” Jia, PhD, postdoctoral scholar of the year, Katie Brown, PhD, co-chair of the Scientific Symposium, Candace Grisham, MS, PhD, co-graduate student of the year, Xiaopeng Sun, PhD, co-graduate student of the year, Jared Rhodes, co-chair of the Scientific Symposium, and Ben Ho Park, MD, PhD, director of Vanderbilt-Ingram.
  • Joshua Bauer, PhD, talks with Nourhan Aboomar about her research poster.
  • Cancer patient Easton Reeder (center) who has undergone surgery and chemotherapy for pilocytic astrocytoma — a type of brain tumor — shared about his experiences living with cancer. He received a jersey signed by the Vanderbilt Commodores baseball team, including pitchers Cody Bowker, left, and Connor Fennell.
  • Candace Grisham, MS, PhD, co-graduate student of the year, speaks about her research involving treatment challenges for tumors that develop within the membranes surrounding the brain and spinal cord.
  • Lili Liu, PhD, (right) and Huy Le Duc, PhD, chat in front of Duc’s research poster.

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This is a phase II study to evaluate the outpatient administration of Teclistamab or Talquetamab in Multiple Myeloma patients
The purpose of this study is to compare how long the participants are disease-free (progression-free survival) and and the length of time until a participant dies (overall survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or metastatic colorectal cancer who have previously received chemotherapy.
The objective of this expanded access protocol is to provide access to Out Of Specification (OOS) AMTAGVI treatment to patients.
This study is being done to answer the following question: Can the chance of lung cancer growing or spreading be lowered by adding targeted radiotherapy to the usual combination of drugs? This study is being done to find out if this approach is better or worse than the usual approach for lung cancer. The usual approach is defined as the care most people get for non-small cell lung cancer.

Study reveals efficacy of nicotinamide for skin cancer prevention 

The dietary supplement nicotinamide has been recommended by dermatologists for people with a history of skin cancer since 2015, when a clinical study with 386 participants showed that those who took the vitamin B3 derivative developed fewer new occurrences. 

However, data to validate those findings in a larger study group has been lacking because nicotinamide can be purchased over the counter without being entered into patients’ medical records.

In a new study published Sept. 17 in JAMA Dermatology, researchers found a way to get that data by analyzing records from the Veterans Affairs Corporate Data Warehouse. Nicotinamide is on the VA’s official formulary, so the researchers checked the outcomes of 33,833 patients for their next skin cancer diagnosis following baseline treatment with 500 milligrams of nicotinamide twice daily for longer than 30 days. They looked for occurrences of basal cell carcinoma and cutaneous squamous cell carcinoma. 

The researchers compared 12,287 patients who received the treatment with 21,479 who did not. Overall, there was a 14% reduction in skin cancer risk. When nicotinamide was taken after a first skin cancer, the risk reduction rose to 54%, but the benefit declined with treatment initiation following subsequent skin cancers. The risk reduction was much larger for squamous cell carcinoma.  

Lee Wheless, MD, PhD
Lee Wheless, MD, PhD

“There are no guidelines for when to start treatment with nicotinamide for skin cancer prevention in the general population. These results would really shift our practice from starting it once patients have developed numerous skin cancers to starting it earlier. We still need to do a better job of identifying who will actually benefit, as roughly only half of patients will develop multiple skin cancers,” said the study’s corresponding author, Lee Wheless, MD, PhD, assistant professor of Dermatology and Medicine at Vanderbilt University Medical Center and a staff physician at VA Tennessee Valley Healthcare System. 

The researchers were also able to ascertain the outcomes of 1,334 patients who were immunocompromised due to having received solid organ transplants. Among solid organ transplant recipients, no overall significant risk reduction was observed, although early nicotinamide use was associated with reduced occurrences of cutaneous squamous cell carcinoma. 

Wheless received research support from a Department of Veterans Affairs grant (IK2CX002452). Other Vanderbilt authors on the study are Katyln Knox, Rachel Weiss, Siwei Zhang, PhD, Lydia Yao, MS, Yaomin Xu, PhD, and Kyle Maas. 

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Study shows magnesium inhibits colorectal cancer carcinogenesis by increasing vitamin D-synthesizing bacteria  

Researchers from Vanderbilt University Medical Center have demonstrated in a precision-based clinical trial that a magnesium supplement increases gut bacteria in humans that have been shown to synthesize vitamin D and inhibit colorectal cancer carcinogenesis.

However, the effect was observed primarily in females — an outcome that the researchers surmised may be attributable to the role that estrogen plays in shifting magnesium from circulation into cellular uptake.

Intestinal microbiome data and colonoscopy results were analyzed from participants who were randomized by whether they had the TRPM7 genotype, which plays a crucial role in regulating magnesium and calcium uptake.

Previously, the investigators showed in the same randomized trial that magnesium enhances the synthesis of vitamin D and increases the blood levels of vitamin D. The findings from the current study suggest that magnesium also increases the gut synthesis of vitamin D, which does not go to the blood and takes effect locally.

These results from the Personalized Prevention of Colorectal Cancer Trial were published Sept. 12 inThe American Journal of Clinical Nutrition. 

Qi Dai, MD, PhD
Qi Dai, MD, PhD

“Our previous study showed magnesium supplementation increased blood levels of vitamin D when vitamin D levels were low,” said Qi Dai, MD, PhD, professor of Medicine. “The current study reveals that magnesium supplementation also increases the gut microbes which have been shown to synthesize vitamin D in the gut without sunlight and locally inhibit colorectal cancer development.”

The participants were divided into two arms, one that received the magnesium supplement and another that received a placebo. Their gut microbiome was analyzed from stools, rectal swabs and rectal tissues. Among participants with adequate TRPM7 function, the magnesium supplement increased Carnobacterium maltaromaticumand Faecalibacterium prausnitzii, which were previously found to work synergistically to increase vitamin D and decrease colorectal carcinogenesis. Among those with inadequate TRPM7function, the magnesium supplement reduced the abundance of F. prausnitziiin rectal mucosa.

Among 236 participants who all had a history of colorectal polyps, 124 underwent colonoscopies after completing the trial with a 3.5-year median follow-up time. A higher abundance of F. prausnitzii in rectal mucosa was associated with an almost threefold increase in developing additional polyps.

The findings suggest that magnesium supplementation treatment may decrease colorectal cancer risk in individuals with inadequate TRPM7function. All together, these findings provide new insights into the interplays between nutrition and gut microbiome contributing to colorectal carcinogenesis and establish the foundation for a precision-based strategy for prevention of colorectal cancer in high-risk populations.

The researchers received support from the National Cancer Institute (R01 DK110166, R01 CA149633 and R03 CA 189455) and the Vanderbilt-Ingram Cancer Center Endowment Fund. Dai and Martha Shrubsole, PhD, Ingram Professor of Cancer Research and research professor of Medicine, are principal investigators of the grant that funded the microbiome research from the National Institute of Diabetes and Digestive and Kidney Diseases (DK110116).

Other major Vanderbilt authors on the study include Elizabeth Sun, Xiangzhu Zhu, MD, MPH, Reid Ness, MD, MPH, Harvey Murff, MD, MPH, and Lei Fan, MD, PhD. The first author, Elizabeth Sun, a medical student at Vanderbilt University School of Medicine, was elected for an Early Investigator Travel Award, a young investigator lightning talk, and an in-person poster presentation at the Precision Nutrition Forum and PREDIMED Omics Symposium 2025 held by Harvard University.

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