[INTERVIEW] Novel immunotherapy gives hope to blood cancer patients

A novel immunotherapy may offer hope for blood cancer patients with no previous options. PeproMene Bio's BAFF-R CAR-T treatment is showing promising results with no side effects.

Dr. Larry Kwak, the scientific founder of PeproMene Bio and deputy director of City of Hope's comprehensive cancer center, during a press interview on Oct. 12 in central Seoul. [PEPROMENE BIO]

A promising novel immunotherapy may provide fresh hope for blood cancer patients who have previously been left with no options.

Dr. Larry Kwak, an award-winning oncologist and scientific founder of Irvine-based PeproMene Bio, believes that the company's clinical-stage chimeric antigen-receptor bearing T cells (CAR-T) therapy will ultimately replace the current CAR-T treatments targeting B-lymphocyte antigen CD19, such as Novartis' Kymriah.

“There's about 60 percent relapse from [patients who received] CD19 CAR-T,” the Korean American physician told the Korea JoongAng Daily. “So in those patients, the [CD19 CAR-T] initially works, but then eventually the tumor comes back.”

Kwak, deputy director of City of Hope's comprehensive cancer center, was named on TIME magazine’s list of the 100 Most Influential People in 2010, and received the Samsung Ho-Am prize in medicine in 2016, which is the year he founded PeproMene Bio.

CAR-T is a type of advanced immunotherapy that genetically reprograms a patient’s cytotoxic T cells to enable them to recognize and kill cancerous cells. It is considered the most advanced modality in cancer treatment, but the relapse rate among patients who received the currently available CD19 CAR-T remains notably high.

Those patients who failed in CD19 CAR-T are PeproMene Bio's primary target with its B-cell activating factor receptor (BAFF-R) CAR-T treatment, said Kwak.

“I've been doing cancer immunotherapy for 30 years, and I've never seen anything like the BAFF-R CAR-T cells,” he said.

“The ideal cancer drug is a drug that has no side effects, and works 100 percent of the time, and that's what we are seeing with the initial results. It's a small number of patients so far, but at the lowest dose, we are seeing no side effects, and maximum effects.”

In its phase 1 clinical trial, PeproMene Bio noted complete responses in three blood cancer patients who were administered the BAFF-R CAR-T cells, two of whom had previously undergone CD19 CAR-T treatment yet experienced a relapse. The company cited BAFF-R antigens being a requirement for B-cell survival as the reason behind the BAFF-R CAR-T treatment's high potential and efficacy. Unlike CD19, tumor cells cannot escape immune responses.

The Korea JoongAng Daily sat down with Kwak on Oct. 12, following PeproMene Bio’s press and investor conference on the company’s phase 1 clinical study results of the CAR-T therapy.

The following are edited excerpts from the interview.

Q. How is CAR-T therapy different from other modalities such as antibody-drug conjugates (ADC) therapy? Is it commercially competitive compared to other options?

A. Kwak:One difference is that you only have to give CAR-T cells to a patient once, whereas in ADC, you have to give the treatment every month, sometimes for two years. Another big difference is that the CAR-T cell is much more potent, so the responses are deeper, meaning more complete and long-lasting responses. With the ADCs, if you stop the treatment, the disease will come back.

Everybody thought that because you have to make one drug for every patient, it would be a limitation for CAR-T treatments, but it turned out not to be the case. Even in the United States, Medicare covers CAR-T cells, so I think it has now become a much more commercially favorable environment for companies to develop CAR-T treatments.

Patients who had previously received CAR-T therapy in the clinical trial were chosen. Was the scientific rationale behind this to ensure a better efficacy of PeproMene’s BAFF-R CAR-T for that kind of patient?

Patients in the U.S. now have access to CD19 CAR-T, but patients who got the CD19 CAR-T treatment and failed, don’t have any options anymore.

So that's why we chose to pick that population — that’s the question, the unmet medical need that we are trying to address. Could this BAFF-R CAR-T be the answer for those patients who failed the existing CAR-T?

Ultimately, we do think one day that BAFF-R CAR-T will replace CD19 CAR-T.

What are your insights on the current situation and the future of CAR-T technology?

What I see is the commercial barrier. It will cost less and less as faster and cheaper manufacturing methods are developed, just like the case of mRNA Covid-19 vaccines, which were manufactured much faster than the traditional protein vaccine. So I think those kinds of manufacturing advances are going to happen and it will make the treatment much cheaper, and therefore more accessible to a bigger number of people.

The Korean government recently announced that it will launch its own version of the ARPA-H, a U.S. agency aimed at driving high-risk, high-return innovation. How do you assess the government’s latest move?

I was really happy to see that because what I observed working with Korean biotech companies, consulting for several of them, is that they are not willing to take risks.

New drug development requires risk because eight or nine out of 10 new drugs will end up not working. So I have been disappointed for years with Korean pharmaceutical companies because they tend to focus on generic drugs, the lowest level of innovation.

To really make big advances, you need to be willing to take risks and it's important for the Korean people and the nation because many global big pharmaceutical companies will not bring their drugs here due to the small market size. So Korea needs to have its own homegrown biotech innovation to make more advances, and not rely on global pharmaceutical companies to come here.

What is your ultimate goal as a researcher and physician?

When I was in high school I had a summer job in a hospital laboratory. The director of the laboratory was a pathologist and after I was done with menial tasks at the end of the day, he would invite me to his office to look at slides of cancer cells under the microscope. He would point out every once in a while that there are some normal immune cells in the cancer cells. He challenged me to think about why they are there, and whether we can use them some day to fight cancer.

And so that's the dream that I've been pursuing ever since — my aspirational goal is to cure one type of cancer, not all cancers, because everyone's going to be different.

BY SHIN HA-NEE [shin.hanee@joongang.co.kr]