Bispecific Antibodies in Cancer

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Bispecific antibodies, as the name suggests, simultaneously target 2 or more tumor antigens on the same or separate cells to disrupt cancer development or progression. Others engage and tether cancer cells and immune cells together to increase cancer-cell destruction.

No matter the strategy researchers take, however, interest in these bioengineered antibodies has been rekindled by the striking success seen in the treatment of some cancers with immunotherapy — notably, checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapy — in the past few years.

“Bispecific antibodies were stalled for a bit, but in this new era of immunotherapy, there’s definitely renewed interest,” said Nikhil Munshi, MD, a medical oncologist at Dana Farber Cancer Institute and director of basic and correlative science at the Jerome Lipper Multiple Myeloma Center in Boston, Massachusetts. “And, we have newer, more modern methodologies that have propelled the field forward.”

An estimated 50 clinical trials using bispecific antibodies for various malignancies are now underway, while biotechnology companies and academic labs purportedly have hundreds of different products in development and awaiting testing.1

Still, the US Food and Drug Administration (FDA) has approved only 1 bispecific antibody with a cancer indication so far, underscoring the need for further research, before these targeted biologics can emerge as viable and less costly alternatives to other types of immunotherapy that are highly tailored to an individual’s cancer.

In July 2017, the FDA approved Amgen’s bispecific antibody, blinatumomab (Blincyto) for acute lymphoblastic leukemia (ALL) in adults and children with advanced disease.Blinatumomab targets and binds 2 proteins, one, CD19, that is found on the surface of B-lineage cells and the other, CD3, that is found on T cells — essentially bringing the 2 in close enough proximity that T cells better recognize leukemic cells to kill them.

Other investigators are using similar tacks in creating these dual-targeting agents.

Researchers at The Ohio State University Comprehensive Cancer Center in Columbus, for example, used an approach comparable to blinatumomab in a humanized mouse model for multiple myeloma, according to Ilan Zipkin, PhD, a vice president at the Parker Institute for Cancer Immunotherapy in San Francisco, California. But the investigators extended the approved drug’s approach, he says, by tethering a common tumor antigen in this cancer, CS1, to a receptor, NKG2D, expressed on several types of immune system cells that kill.

Dr Zipkin wrote in an email that the Ohio researchers “are showing activity with a bispecific that promotes several different cell types to kill the myeloma cells,” including, importantly, natural killer cells. Results of that study were among those highlighted at the American Association for Cancer Research Annual Meeting in Chicago, Illinois, earlier this year.3

In multiple myeloma, CS1 is considered a well-defined antigen, which investigators already are targeting with CAR-T therapy, according to Dr Munshi. “But this group put it together with NKG2D, an interesting molecule, which is scientifically intriguing,” he says. “They showed a good response.”

Nevertheless, for this and other bispecific antibodies to work best in patients, Dr Munshi said there is a prerequisite: a functional immune system must be present. CAR-T therapy has a clear advantage over bispecific antibodies right now, he explained, because “you can overcome some of the immune-suppressive environment” that occurs. Still, given the prohibitive costs of CAR-T’s customized approach, Dr Munshi and others believe bispecific antibodies could provide an economical alternative for patients in the future, broadening access to treatment.

Michael Verneris, MD, director of bone marrow transplant and cellular therapy at Children’s Hospital in Denver, Colorado, also sees an evolving role for these next-generation designer antibodies. Although the need for intact immunity and a lack of persistent therapeutic effect pose barriers right now, he says, bispecific antibodies have considerable upside, as well.

“These are modular, relatively small molecules that can be quick to produce,” he said. “If ‘A’ and ‘B’ don’t work, you can keep on mixing and matching until you can create whatever you want.” One obvious advantage to patients is that if complications arise, they can be addressed quickly, he said.

“The great hope is that these will be in the deck of options for patients,” as an integral part of a multipronged strategy against cancer, Dr Verneris said.

Although no bispecific monoclonal antibodies in the first-line setting exist yet, he is confident that clinical trials in patients with early-stage cancers eventually will take place, when chemotherapy damage to their immune systems is not so extensive.

Dr Verneris said he has watched unlikely strategies in immuno-oncology gradually unfold successfully before, and the same could happen with bispecific antibodies. “It’s been hugely gratifying to see some of these ideas come raging forward.”

References

  1. Krishnamurthy A, Jimeno A. Bispecific antibodies for cancer therapy: a reviewPharmacol Ther.2018;185:122-134.
  2. FDA grants regular approval to blinatumomab and expands indication to include Philadelphia chromosome positive B-cell. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm566708.html. Updated July 12, 2017. Accessed August 20, 2018.
  3. Chan, WK, Kang S, Youssef Y, et al. A CS1-NKG2D bispecific antibody collectively activates cytolytic immune cells against multiple myelomaCancer Immunol Res.2018;6(7):776-787.

 

Susan Jenks

August 22, 2018

Click here for full article:  Cancer Therapy Advisor

Daytona News Journal on Nutronco, Dr. Acs, and PowerOnco

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Nutrition vs Treatment

New Supplement May Be The Answer For Chemo Patients

By Nikki Ross

nikki.ross@news-jrnl.com

06/25/2018

As if chemotherapy isn’t hard enough on its own, patients who undergo this course of cancer treatment also have the added struggle of maintaining a nutritious diet.

Now these patients have access to a nutritional supplement specifically designed to give them the nutrients they need when they find it hard to keep down their meals.

“This is the baby we have been working on for two years,” said Dr. Peter Acs, founder and chief medical officer for Nutronco.

The goal for the supplement, Poweronco, is to improve nutrition, rebuild muscle, support the immune system, decrease inflammation and overall to help with chemotherapy side effects. The product was developed and produced by the emerging nutrition company Nutronco.

“It bothered me to see patients struggle to find a nutritional product that they could keep down,” said Acs, who also is a board-certified hematologist and oncologist.

“I had been wanting to do something like this for years and now it’s here.”

Poweronco is a chocolate flavored powder that chemotherapy patients can mix in six to eight ounces of water once or twice a day.

It costs $99.99 for a one month supply which equals $3.75 per serving. It can be purchased on Nutronco’s website. They are hoping to soon have it available in nutritional stores.

“This is something that they can drink easily because it dissolves nicely in the water,” said Hayes Milani, CFO of Nutronco.

“It’s filling but we also always recommend taking it with a healthy diet.”

Milani and Acs stress that Poweronco is not an alternative treatment though it does help patients tolerate their chemotherapy treatment better then those who don’t take it.

“The main thing for patients undergoing chemotherapy is to eat well and maintaining weighing during treatment,” said Padmaja Sai, hematologist and oncologist at Florida Hospital. “If they are not really getting enough nutrients through their diet then we recommend patients take some nutritional supplements.”

There are several factors that contribute to nutritional deterioration in chemotherapy patients.

The treatment causes cells to stop multiplying in the body, even the good ones.

Patients who undergo chemotherapy may be subject to bed rest and, according to Acs, patients on bed rest lose 10 percent of muscle mass per week.

“Fifty to 80 percent of cancer patients have nutritional issues,” Aces said.

“Forty percent of cancer patients die from malnutrition or cachexia.”

The supplement contains ingredients that help to combat the negative side effects of chemotherapy treatment. It has nucleotides that boost the immune system, help with healing and decreases the chance of infection.

It also contains probiotics that help with the development and stability of the good bacteria in the body, strengthens the immune system and prevents the chemotherapy side effect of diarrhea.

“I don’t see anything wrong with it as long as it ties into everything else we mentioned maintaining a healthy lifestyle, organic diet, no smoking and limited alcohol intake,” Sai said. “As far as I know there is no other nutritional supplement that caters to chemotherapy patients.”

Prebiotics also have been added to the supplement to give good bacteria the surface to grow. Ginger and other ingredients are also there to reduce nausea. It also includes protein. “Many oncologists will be skeptical,” said Dr. Michael Epitropoulos, oncologist, chiropractic and natural medicine physician.

“They have checked for a reaction between the ingredients and the chemotherapy and found that it will not harm treatment like other supplements.”

Acs said his main goal in developing this supplement is to help chemotherapy patients have a more positive outcome. “This is to help them take some control over their nutrition,” Acs said. “And to help them fight against cancer.”

For information on Nutronco and their products, visit nutronco.com.

To contact Dr. Peter Acs, call 352-672-4403.

To contact Hayes Milani, call 352-278-2526.

To contact Dr. Michael Epitropoulos, call 386-274-2520.

Cancer Cells and Normal Cells

What Are the Differences Between Cancer Cells and Normal Cells?

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Cancer cells are very different from normal cells. These differences typically allow them to escape from under control and grow wildly. Not only do they grow uncontrollably, but they are aggressive and become invasive. Normal cells will mature into specialized cell types with specific functions, whereas cancer cells do the opposite: they become less and less specialized as they lose control and become more aggressive. The way we describe how much they differ from normal cells is called: grade. A cancer that is low grade resembles more to its normal counterpart than a high grade disease (for more information see blog: What is Tumor Grade?). In addition to cancer cells’ ability to multiply without control, they are also able to ignore signals that normally tell cells to stop dividing or to die. Cancer cells may produce and secrete growth factors and other hormones that will stimulate normal cells to act in favor of the cancer, like forming blood vessels. Another important feature of cancer cells is that they may change in ways that help them evade the immune system and become “invisible” to the body’s natural ability to remove abnormal cells. Luckily, some of these features we can use in the fight against cancer. The rapid growth of cancer cells is the reason why we can use chemotherapy that typically targets dividing cells and due to the hormone dependence of some cancers, we can use hormonal manipulation.

Peter Acs, MD, PhD – Medical Oncologist

Updated 11:20 AM ET, Monday May 28, 2018

Tumor Grade Cancer

What Is Cancer?

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Cancer develops when cells start growing without control and spread into surrounding tissues. This can happen in any type of cell in any organ. Cells normally grow and divide to form new cells as the body needs them, and when cells become old or damaged they die. In cancer cells this mechanism gets impaired and cells continue to grow even when they should die or when they are damaged. The resultant tumor becomes malignant, and called cancer, when these abnormal cells start to grow into surrounding tissue. Eventually, some cells will acquire the ability to travel to distant places in the body and form new tumors at these locations.  Once a cancer diagnosis is made the extent of the disease must be assessed. This is called staging. Typically stage I cancers are small and localized, stage II ones are larger but still localized. Stage III cancer has moved to lymph nodes, whereas stage IV disease means disease in distant organs. This is called metastatic cancer. Staging determines treatment options. Stage I cancer is usually curable with surgery, while the treatment of choice for stage IV cancer is systemic chemotherapy.

Peter Acs, MD, PhD – Medical Oncologist

Updated 4:30 PM ET, Monday April 23, 2018

Tumor Grade Cancer

What Is Cancer Cachexia?

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Cancer cachexia is a multifactorial condition characterized by systemic inflammation and severe wasting of skeletal muscle, with or without wasting of adipose tissue (fat). It causes considerable morbidity and mortality in these patients. Cachexia occurs in 50–80% of cancer patients and it has been identified as an independent predictor of treatment failure and decreased survival. There are several factors that contribute to nutritional deterioration, muscle wasting and worsening weight loss in cancer patients. The process is a vicious cycle caused by weakening of the immune system, further inflammation, infection, worsening weakness, widespread metabolic changes, debilitation which collectively contribute to an increase in fatigue, poor physical function, diminished quality of life and ultimately death. Improving nutrition, rebuilding muscle mass and strength, supporting the immune system, decreasing inflammation help prevent this from happening and enables us to treat the underlying malignancy more effectively.

Peter Acs, MD, PhD – Medical Oncologist

Updated 11:00 AM ET, Tues April 17, 2018

Tumor Grade

Cancer and Xylitol

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Xylitol is a natural sugar alcohol that can be used as a food sweetener. It is permissible for cancer patients since it is not fermented by cancer like glucose, and a significantly smaller percentage is absorbed in the GI tract. Xylitol even reduces intestinal glucose absorption. Furthermore, xylitol can alleviate treatment side effects like dry mouth and mucositis. It also has antimicrobial properties especially against encapsulated organisms like Pneumococcus, and was shown to have anticancer effects in lung cancer cells. A study of lung cancer cell lines demonstrated that xylitol has a dose-dependent inhibitory effect on cell proliferation. A different study also demonstrated that xylitol has an antiproliferative effect in vitro. In this study, normal cells and oral squamous cell cancer cell lines were treated with glucose or partial substitution of glucose with xylitol. Partial substitution of glucose with xylitol resulted in decreased cell proliferation. A metabolite of xylitol, D-xylulose, further enhanced the antiproliferative activity of xylitol. In addition, there are no data to suggest that xylitol is carcinogenic or is associated with an increased risk of cancer.

Peter Acs, MD, PhD – Medical Oncologist

Updated 1:30 PM ET, Mon April 9, 2018