A less toxic treatment for cancer and other diseases

[00:00:00] Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. Bispecific antibody therapy has generated excitement among cancer researchers in recent years as a way to treat certain cancers. Today I am talking with a doctor who will help us understand the promise of these bispecific antibodies. Dr. Krishna Ghimire is an assistant professor of medicine at Upstate specializing in hematology and medical oncology. Welcome to "The Informed Patient," Dr. Ghimire.

[00:00:38] Krishna Ghimire, MD: Thank you for having me, Amber.

[00:00:40] Host Amber Smith: I'd like to start by asking you to tell us what antibodies are and where they fit in with cancer therapies.

[00:00:49] Krishna Ghimire, MD: Well, that's an excellent question, which is a very relevant nowadays in terms of treatment for cancer patients. An antibody is a type of protein produced by the immune system in response to the presence of the foreign substance, what we call antigen in medical terms. So these antibodies, or protein, are a key part of the immune system defense mechanism, which are primarily produced by the white blood cells in our body.

And in terms of where they fit with the cancer therapies, let me take you a little bit to the basics of how this protein looked like. They look like a shape of a Y, the English alphabet's Y, where the tip of the Y binds to the foreign substance, for example, cancer, and the stem of the Y attaches it to the immune system and helps the immune system to recognize them and activate them.

So these antibodies, when they bind to the cancer cells, they block the growth of the cancer cells. They attack and destroy them. That's how we are using these antibodies in the space of the cancer treatment.

[00:02:16] Host Amber Smith: So these antibodies, our bodies make these normally?

[00:02:20] Krishna Ghimire, MD: That is correct. The antibodies are made by the bodies normally. They're normally called polyclonal antibodies. So they have ability to attack different infections, different foreign substances. But some of the antibodies that we use in the therapies are called therapeutic antibodies, which are designed in such a way that they attack to particular targets, for example, cancer. In some conditions they can attack, too, some autoimmune conditions like rheumatoid arthritis, there may be some particular targets. So these are, in a way, very focused and, in a way, laser guided type of approach, where those antibodies are produced to attack certain targets that we want them to attack to and minimize the other off target side effects.

[00:03:18] Host Amber Smith: So let me ask you this. If a person has cancer, is their body making enough of these antibodies on its own?

[00:03:27] Krishna Ghimire, MD: Our immune system is designed in such a way that when somebody has a cancer there's a mechanism for our body to kill them by the immune system.

When somebody develops the cancer, while they are developing it, that mechanism is not working anymore. Somehow that system is inactive. So we try to use our body's immune system and make them more active, make them recognize the cancer and kill the cancer with the help of the antibodies.

[00:04:04] Host Amber Smith: Now I've also heard of something called monoclonal antibodies. What is that?

[00:04:10] Krishna Ghimire, MD: Monoclonal antibodies are produced by a type of a cell, what we call clonal cells, that is only one type of the cells. Those monoclonal antibodies are very specific antibodies we target to specific targets, for example, cancer. One example, let's say if we have monoclonal antibodies for lung cancer, it's going to work only for the lung cancer. It's not going to work for the colon cancer, for example.

So these are very uniquely designed proteins to target the specific type of the cancer, which is more of like a personalized cure for our patients. Specific cancer patients get a specific type of antibodies, and that antibody cannot be used for other type of cancers.

[00:04:57] Host Amber Smith: So what is a bispecific antibody?

[00:05:00] Krishna Ghimire, MD: Oh, that's even more interesting. Bispecific antibodies are a special type of antibodies where there are two different types of antibodies binded together. So they have two different arms, in a way. So one arm is going to attach or bind to the cancer cells. The other arm is going to bind to the immune cells. So those immune cells then get activated. Those activated immune cells attack the cancer and help them to destroy the cancer.

[00:05:38] Host Amber Smith: So are the bispecific antibodies made with the help of real antibodies from the body? Are they then worked on in a lab?

[00:05:48] Krishna Ghimire, MD: So these bispecific antibodies are designed in the lab. They are designed in such a way that they have those specific targets that we like to attack upon.

That's why those specific antibodiesare manufactured in the lab, and they are shipped to our cancer centers where we can infuse to our patients and help them fight those specific type of cancers.

[00:06:17] Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host Amber Smith. I'm talking with Dr. Krishna Ghimire. He's a hematologist oncologist at Upstate.

So how many bispecific antibodies have received FDA approval for use?

[00:06:32] Krishna Ghimire, MD: As of now, when you and me are talking, there are more than a dozen of antibodies, already approved by federal drug regulation agencies so far. There are many, many more in the pipeline as well.

In terms of the numbers of antibodies I just mentioned, there are hundreds of those in the pipeline. They are in the early stage of development. And they have to go through the drug approval process and different phases of the clinical trials. We expect that those clinical trials will mature and hopefully, they'll have good results, and those treatments will be valuable for our patients in near future.

[00:07:13] Host Amber Smith: Do bispecific therapies work on solid tumors or blood cancers?

[00:07:19] Krishna Ghimire, MD: Bispecific antibodies can work for both solid tumor as well as blood related cancers. And as well as there are other conditions besides the cancers where they have also been used for autoimmune conditions, bleeding related problems, and also in some diabetes related complications.

So it's use is growing day by day, and it's a very exciting time in this field, especially in the cancer field. How these therapies have evolved over time and how remarkable the response we have seen while going through these therapies for our patients. We have seen multiple, multiple, multiple lines of therapies in the past.

[00:08:02] Host Amber Smith: Do you have patients who are treated with bispecific antibodies?

[00:08:06] Krishna Ghimire, MD: Absolutely. We do have patients who have undergone bispecific antibodies for blood related cancers as well as solid tumors.

And, these patients have been through many lines of chemotherapies in the past, and their outcome remains very dismal after so many lines of therapies. The promise that these bispecific antibodies has given to our patients with the minimal toxicity and manageable toxicity is very, very promising.

[00:08:39] Host Amber Smith: What do you say to someone if they're considering taking a bispecific therapy? What do they need to think about ahead of time?

[00:08:47] Krishna Ghimire, MD: I think it is very important to consider them ahead of time so that you can plan accordingly. Some of the therapies do take time to bring it to you, to the cancer center.

So, first of all, we need to discuss with our peer provider whether or not somebody's eligible to get those bispecific therapies. And for someone who qualifies for the bispecific therapy, there are a few things that we need to consider that will help us to navigate the treatment process.

First of all, understanding the treatment. So we increase our patients to ask the providers how the therapy works, why it is used, what are the benefits of using those therapies, and what are the toxicities, what are the risk and what are the alternatives of the treatment? And also we need to know about the side effects, the common side effects, of those therapies and how to treat those side effects when somebody do develop those side effects.

And also, it is very important that supportive care is also equally important in those patients who have planned to undergo bispecific antibodies -- staying very well hydrated, eating well, having a good rest, and having both social support as well as physical support is very, very important. So having those support ahead of time when you plan early would be a lot easier to manage. And also it's very important to look for some clinical trials, also some financial assistance programs, insurance coverage, all those things sometimes can be a hindrance for timely therapy. So that's why it's very important too look for those things early on in the treatment. And you can get the treatment on time when you need them.

[00:10:49] Host Amber Smith: So is the treatment intravenous, or is it through, do you take pills? How does it work, in general?

In general, those bispecific antibodies are intravenous therapies, but recently there have been some approval for injections, subcutaneous injection medications as well. So far, there is no pill available as a bispecific therapy. Hopefully with the advancement in science in the future, hopefully we will like to see those pills as well, which will be a lot easier to administer, for the healthcare provider as well as to our patients as well.It sounds like bispecific antibodies are not the first line therapy. Are these generally saved for people who've already tried some other treatment for their cancer?

[00:11:41] Krishna Ghimire, MD: So some of the bispecific therapies have been moving to the earlier and earlier lines of therapy as well, in some of the blood related cancers.

But in solid tumors, they have been on later lines of therapies. So it all depends upon what type of the diagnosis you have and what type of therapiesyou are going to get. So most of the bispecific therapies have been used in later lines of treatment so far, but because the patients are getting such a good response to the therapies, and the toxicities are much, much manageable than the other chemotherapy drugs, so they have been moving to the earlier and earlier and earlier lines of treatment.

[00:12:18] Host Amber Smith: Are they considered potentially curative?

[00:12:22] Krishna Ghimire, MD: So it's very interesting. bispecific therapies so far is not a curative treatment. But with the treatment we can control the disease and control the growth of the cancer and also potentially get a deep remission, hopefully a longer period of time. But so far it is not a curative treatment.

[00:12:44] Host Amber Smith: How do you expect these therapies to evolve over the coming years?

[00:12:51] Krishna Ghimire, MD: I think some of those therapies have some potential side effects, obviously. So, having more and more therapies, newer therapies, more effective therapies, with less toxicity that we're hoping. And some of the therapies are given for a long duration as well, and we are hoping shorter duration therapies and longer interval inbetween the therapies. So these are some of the things I think, as the science evolves, hopefully new drugs will have those qualities we just discussed about.

[00:13:21] Host Amber Smith: Well, Dr. Ghimire, I appreciate you making time for this interview. Thank you.

[00:13:27] Krishna Ghimire, MD: Thank you so much for having me.

[00:13:29] Host Amber Smith: My guest has been hematologist oncologist, Dr. Krishna Ghimire from Upstate. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe, with sound engineering by Bill Broeckel and graphic design by Dan Cameron. Find our archive of previous episodes at upstate.edu/informed. If you enjoyed this episode, please tell a friend to listen too. And you can rate and review "The Informed Patient" podcast on Spotify, Apple podcasts, YouTube, or wherever you tune in. This is your host, Amber Smith, thanking you for listening.