New Monoclonal Antibody Offers Hope In the Fight Against Ovarian Cancer

“Kellogg, an associate professor of pathology and laboratory medicine at the Brody School of Medicine at [East Carolina University] ECU, created the antibody, called DS-6, that attaches to cancer cells in her laboratory at ECU. DS-6 will serve as a delivery vehicle for a highly potent cell-killing agent developed by ImmunoGen specifically for delivery to cancer cells by antibodies. The antibody latches on to tumor cells and enables the whole compound – the antibody and the attached cell-killing agent – to enter the cancer cell. Once inside, the cell-killing agent becomes activated and kills the tumor cell as it divides.”

“A discovery by an East Carolina University pathologist might be a breakthrough in an evolving class of drugs used to fight cancer.

Dr. Anne Kellogg has developed a monoclonal antibody that could play a vital role in treating the most common form of ovarian cancer, breast cancer and other cancers. She is working with two major drug firms, ImmunoGen Inc. and sanofi-aventis, that have expertise in formulating antibodies into cancer therapies and taking them to clinical trials in humans.

Kellogg, an associate professor of pathology and laboratory medicine at the Brody School of Medicine at ECU, created the antibody, called DS-6, that attaches to cancer cells in her laboratory at ECU. DS-6 will serve as a delivery vehicle for a highly potent cell-killing agent developed by ImmunoGen specifically for delivery to cancer cells by antibodies. The antibody latches on to tumor cells and enables the whole compound – the antibody and the attached cell-killing agent – to enter the cancer cell. Once inside, the cell-killing agent becomes activated and kills the tumor cell as it divides.

‘We can’t give such a potent chemotherapy agent on its own because it would be too toxic, but if we can link it to an antibody, it goes inside the tumor cell and is released inside the tumor cell, which is really an amazing feat,’ Kellogg said.

The antibody with the cell-killing agent linked to it circulates in the body in an inactive state. The cell-killing agent becomes active only when it reaches the tumor cell, so ImmunoGen refers to its technology as Tumor-Activated Prodrug, or TAP, technology. Sanofi-aventis has rights to develop specific anticancer agents using ImmunoGen’s TAP technology and is in charge of advancing the TAP compound containing the DS-6 antibody licensed from ECU into human clinical testing.

Monoclonal antibodies are manufactured proteins, produced from a single parent cell, that bind to a specific substance. They can be used to detect or purify that substance and are widely used in hospital and pathology laboratories as components of diagnostic tests. Monoclonal antibodies gained attention as a possible way to treat cancer in the 1980s. In the 1990s, scientists refined techniques to expand their usefulness as therapeutics by making subtle changes to the antibodies so the human body would not reject them as foreign tissue. One of the best-known monoclonal antibodies is trastuzumab, sold under the brand name Herceptin and used to treat breast cancer.

Kellogg began working with monoclonal antibodies in the early 1990s looking for ones pathologists could use to diagnose cancer. A few years later, working with Dr. Diane Semer, a gynecologic oncologist formerly with ECU, Kellogg turned her attention to identifying an antibody that could not only recognize tumors but also be useful in treating them. She isolated DS-6 in the late 1990s and then began characterizing the antibody for its ability to recognize various types of cancer with the help of Dr. Nancy Smith, a former ECU pathologist.

‘Drugs that are developed from monoclonal antibodies are potentially more specific for tumors and risk less in the way of toxicity to the patient,’ said Dr. Adam Asch, associate director of the Leo W. Jenkins Cancer Center at ECU. Kellogg added that the treatment could have benefits even if it falls short of curing cancer. ‘You may be able to convert cancer to a very chronic disease you can treat if we can provide oncologists with a wider array of treatment options,’ she said.

‘This has been an amazing education for me and personally very rewarding to get a ringside seat in seeing the complex process of drug discovery and development take place. It has also demonstrated how well academia, biotechnology and pharmaceutical companies can work together in this process,’ Kellogg said.

Kellogg’s research has been funded in part by ECU and the Department of Pathology and Laboratory Medicine. ‘We feel we made a wise investment that will help advance the treatment of cancer by providing funds for Dr. Kellogg’s research,’ said Dr. Peter Kragel, chair of the department. Future grants from ImmunoGen and sanofi-aventis are under discussion.”

[Quoted Source: New Antibody Offers Hope for Treating Ovarian, Breast Cancer, NewsWise Medical News Release dated May 22, 2008.]

6 thoughts on “New Monoclonal Antibody Offers Hope In the Fight Against Ovarian Cancer

  1. My sister was in this blind trial, and got the placebo. Had to drop out when she could no longer tolerate the chemo (blood clots) Now she’s been given 2 months – does anyone know when this drug will be FDA approved, please someone give me good news! Is it possibly available in other countries? I’ll fly her out in a minute if that’s the case – Please help

    Like

    • Dear Julie:

      We are so sorry to hear about your sister. As you know, the clinical trial drug that you are referring to is SAR566658 and it is manufactured by Sanofi-Aventis. The clinicaltrials.gov identifier I.D. associated with the SAR566658 is NCT01156870.

      SAR566658 is currently in Phase 1 clinical trial development. Generally, drugs are approved some period of time after completion of Phase 3 clinical trial testing. For a general overview of the FDA drug approval process, click here.

      Outside of a clinical trial, access to the drug can be obtained through an FDA program known as “expanded access.” Expanded access, sometimes called “compassionate use,” is the use of an investigational drug outside of a clinical trial to treat a patient with a serious or immediately life-threatening disease or condition who has no comparable or satisfactory alternative treatment options.

      FDA regulations allow access to investigational drugs for treatment purposes on a case-by-case basis for an individual patient, or for intermediate-size groups of patients with similar treatment needs who otherwise do not qualify to participate in a clinical trial. They also permit expanded access for large groups of patients who do not have other treatment options available, once more is known about the safety and potential effectiveness of a drug from ongoing or completed clinical trials.

      Just as in clinical trials, these investigational drugs have not yet been approved by the FDA as safe and effective. They may be effective in the treatment of a condition, or they may not. They also may have unexpected serious side effects. For an overview of the FDA expanded access program, click here.

      If the life expectancy statistics provided to your sister are even somewhat accurate (and we hate life expectancy statistics), you and her doctor may not have time to obtain expanded access. This concern raises an important question: Why are you looking to use only SAR566658? Was your sister’s tumor tested previously for any molecular or genetic characteristics that may prove helpful in choosing a new clinical trial drug ? If you really want to find definitive information regarding access to SAR566658, we suggest that you contact Sanofi-Aventis at 1-800-981-2491 and ask for assistance regarding availability of this drug. Our search of http://www.clinicaltrials.gov only produced the clinical trial above (i.e., the trial in which your sister received placebo).

      If Sanofi-Aventis can not provide you with helpful information, you should consider another open ovarian cancer clinical trial or solid tumor trial, assuming your sister can qualify.

      If you have any further questions, please feel free to contact us. Please know that our thoughts and prayers are with you and your sister.

      Best regards,

      Paul

      Like

  2. Any new progress on the monoclonal antibody offering hope to fight Ovarian Cancer? Any closer to clinical trials?

    Thank you.

    v/r,

    Keith Johnson
    Winter Park, FL

    Like

    • Keith,

      I sent an email to Dr. Kellogg at East Carolina University regarding the current development status of the TAP compound containing the DS-6 antibody. I will let you know if I hear back from Dr. Kellogg. In the interim, if you wish to contact Dr. Kellogg directly please free to use her contact information..

      Best,

      Paul

      Like

    • Keith,

      Dr. Ann Kellogg was kind enough to promptly reply to my email request regarding the current development status of the TAP compound containing the DS6 antibody. As far as she knows, DS6 is still in preclinical development by ImmunoGen Inc. and Sanofi-Aventis and is progressing towards clinical trials. Dr. Kellogg no longer participates in the preclinical development of DS6 because significant expertise, possessed by large drug companies, is required with respect to FDA drug development/clinical trial rules and guidelines/standards. In line with Dr. Kellogg’s comment, I should note that the ImmunoGen Inc. website drug “pipeline” chart also shows the TAP compound in preclinical development. As you know, many drugs do not make it out of preclinical development but hopefully this one will in the future. I should also note that Dr. Kellogg would likely be notified if there were any significant development problems with DS6 to date. Such notification has not occurred as of this writing.

      By this comment, I would like to thank Dr. Kellogg for taking the time to respond promptly to our email inquiry.

      Best,

      Paul

      Like

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s