Sunday, August 11, 2013

Amazing Antibodies

Oncology Live published a great article this week on antibodies and their use in cancer treatment.

Of course, Rituximab (Rituxan), my bestest pal, among them, and the article credits Rituxan as being the first of the great anti-cancer antibodies, followed shortly by Trastuzumab, better known as Herceptin, used against breast cancer.  Soon after that come Ibritumomab (Zevalin) and I-131 tositumomab (Bexxar), and then a bunch more. All of those "-mab" endings mean "monoclonal antibodies," of course, and there are a bunch more, with more to come.

The article gives a brief history of MABs, and it's fascinating. I know some things about Rituxan, since we're "besties" and all, but I didn't know about that Chinese Hamster Ovary cells, CHOs, are the most common cell line used to make MABs these days. Or that yeast and algae are being explored as ways to produce  MABs even faster and cheaper. Kind of cool.

There's a nice chart of MABs that have been approved so far, and of a bunch more than are currently in phase III clinical trials. Those in the pipeline include Inotuzumab Ozogamicin, which targets CD22 in NHL (a phase III trial was actually cancelled in May, though other trials are ongoing), and Obinutuzumab (GA101), which has been getting some positive press lately.

I think the most interesting part of this article, though, is the discussion of the ways antibodies are being "redesigned" by researchers, to improve on their effectiveness by overcoming some of their natural limitations. These redesigns include:
  • Conjugates, where antibodies have something added to them, like radiation or chemotherapy. The antibody isn't used to destroy the cell, the way it is with, say, Rituxan, but rather to deliver a deadly payload, as with Zevalin. About half the antibodies being developed are conjugated types.
  • Glycoengineering, where the antibodies are manipulated to change the sugars they contain, which affects how well they bind to their targets. GA-101 is a glycoengineered antibody.
  • Fragmentation, where pieces of antibodies are used, because they penetrate solid tumors better. (Not really relevant to lymphoma, but interesting anyway.)
  • Bispecification, where two different antibodies are combined into one. One example is Blinatumomab, also known as MT103. Very cool antibody; its two arms target different things -- the cancerous B cell, and the healthy attacking T cell. This allows the body's defenses to recognize the cancer cell and take it out. It's in phase II trials right now, and shows some promise.
    Blinatumomab (MT103)
There are a few other redesigns, but these are the most interesting to me. The article will tell you more.

Overall, this is a pretty nice introduction to the amazing world of antibodies.
Inotuzumab ozogamicin
Inotuzumab ozogamici n


Anonymous said...

Thank you Lympho Bob for your up to date information. I have recently been diagnosed with follicular lymphoma Stage 4A indolent. This is all new to me so your clear concise explanations and links to research are invaluable. I have had one treatment thus far with rituxan and Bendamustine and your recent link to the summary studies clarified many questions. I am battling an enlarged spleen and have had two pleural effusion drains since diagnosis and I hope that this combination will also deal with these in short order. Take care and thank you again.

Lymphomaniac said...

Glad I could help! Bendamustine often works well for 4A, so it sounds like a good choice. I know lots of people who have had great success with B + R with stage 4.

Please keep me updated. I'd like to know how things are progressing after another treatment or two (I'm guessing there's probably a scan coming after #3?).

Good luck. I'll be thinking about you.

TLR2 antibody said...

Very informative post on these antibodies. There are several antibodies that have different affects on various cancers. This article makes a good & concise point.