Positive Butterfly News, Immune Tweaking with CRISPR, and Looking to the Future in China
As I reported in a previous blog, not only does the herbicide Roundup cause lymphomas and myeloma, its widespread use on GMO (genetically modified organism) crops has decimated milkweed, an herbaceous perennial and the essential food for monarch butterflies. Since 1990, about 970 million monarchs have vanished.
There is good news: one step at a time, the monarch butterflies are coming back. Here in Los Angeles, a myeloma patient planted milkweed several months ago to attract remaining butterflies. Fortunately, a pregnant female found the milkweed and laid her eggs. When birds began to devour the caterpillars that developed from the eggs, this patient “adopted” about a dozen and brought them to safety indoors to feed on milkweed.
Over a period of weeks, they ate and ate. Then they “glued” themselves upside down in a “J” shape, and the metamorphosis began. The caterpillars wriggled out of their skins and pupated into chrysalises.
One week later, each monarch broke out of its chrysalis shell, uncurled, pumped blood into its wings, and dried off. After a few hours of resting, the butterflies were ready to fly off and meet their friends.
This is the kind of beautiful nurturing necessary to restore the balance of nature. At a time when the US Fish and Wildlife Service acknowledges that “the monarch butterfly is in trouble,” but the Environmental Protection Agency rejects the notion that Roundup and chemical spraying are problems, individual action is required. Perhaps we cannot stop the spraying right away, but increased awareness can help protect everyone, and maybe even save the butterflies.
How cancer cells resist immunotherapy
Another follow-up to last week’s blog is news from the National Cancer Institute’s Nicholas Restifo about how and why cancer cells become resistant to immunotherapy. As I mentioned in a previous blog, “fine tuning” is required to achieve the optimal immune attack against cancer. Researchers in this study used CRISPR technology to create “loss of function” mutations. This resulted in resistance or unresponsiveness on the part of effector/suppressor CD8+ T cells. Of note, one antigen susceptible to such mutations is β₂M (β₂ microglobulin), which is dominant in the cellular biology of myeloma.
Although B2M was not studied further as part of this study, additional work may reveal a role for this and/or additional antigens in immune unresponsiveness in myeloma. It is clear that detailed tweaking will indeed be required to optimize immune therapy approaches. As Dr. Restifo says, “If we can truly understand mechanisms of resistance to immunotherapy, we might be able to develop new therapeutics.”
6th Annual Myeloma Master Class
The IMF’s Myeloma Master Class for Chinese physicians will be held again in Los Angeles next week. This successful program brings students from the top centers in China with emerging myeloma programs to learn the latest about the biology, diagnosis, and treatment of myeloma.
Myeloma experts Drs. Vincent Rajkumar (Mayo Clinic Rochester), Joseph Mikhael (Mayo Clinic Scottsdale), Tom Martin (UCSF), Jonathan Kaufman (Emory University), and Robert Vescio (Cedars-Sinai Medical Center) are this year’s educators. Students will visit the City of Hope myeloma group and transplant center. They will also have a chance to observe in-person patient consultations while attending the IMF Los Angeles Patient & Family Seminar, on Friday and Saturday, August 18 and 19.
This cultural exchange has now produced more than 50 graduates, all of whom passed the examination at the end of the week and returned to China as the local “experts.” Not only has this substantially raised the level of knowledge and care for myeloma patients, the program has helped trigger a range of research initiatives. For example, MRD testing has been set up at several centers in China.
A sign of how rapidly things are emerging in China was seen at this year’s Annual Meeting of the American Society of Clinical Oncology (ASCO), where results with CAR T-cell therapy from China were presented with excellent outcomes and favorable toxicity profile. This placed China right in the center of a very competitive space in which eight or nine companies are vying for priority for “first and best in class” for this new therapy.
As might be expected when moving aggressively forward, missteps can occur. A different group of researchers in China recently had to retract a paper with sequencing results because they sequenced the genome from the wrong type of snails in a gene rearrangement/protein coding analysis.
Still, China will soon be a force to be reckoned with. Well-informed young investigators have access to tremendous biomedical resources, motivation, and funding. Look for more important advances coming from West to East!
Dr. Brian G.M. Durie serves as Chairman of the International Myeloma Foundation and serves on its Scientific Advisory Board. Additionally, he is Chairman of the IMF's International Myeloma Working Group, a consortium of nearly 200 myeloma experts from around the world. Dr. Durie also leads the IMF’s Black Swan Research Initiative®.