What timing! Just when our feature on Max Cooper and lamprey immunology was scheduled for publication, the Japan Prize Foundation announced it would honor Cooper and his achievements.
Cooper was one of the founders of modern immunology. We connect his early work with his lab’s more recent focus on lampreys, primitive parasites with surprisingly sophisticated immune systems.
Molecules from animals with exotic immune systems can be big business, as Andrew Joseph from STAT News points out. Pharmaceutical giant Sanofi recently bought a company focused on nanobodies, originally derived from camels, llamas and alpacas, for $4.8 billion.
Lampreys’ variable lymphocyte receptors (VLRs) are their version of antibodies, even though they look quite different in molecular terms. Research on VLRs and their origins may seem impractical. However, Cooper’s team has shown their utility as diagnostic tools, and his colleagues have been weaponizing them, possibly for use in cancer immunotherapy.
CAR-T cells have attracted attention for dramatic elimination of certain types of leukemias from the body and also for harsh side effects and staggering costs; see this opinion piece by Georgia Tech’s Aaron Levine. Now many research teams are scheming about how to apply the approach to other types of cancers. The provocative idea is: replace the standard CAR (chimeric antigen receptor) warhead with a lamprey VLR.
CRISPR-Cas9 gene editing alleviates Huntington’s in mouse model
— Shi-Hua and Xiao-Jiang Li. This project is progressing, with funding from NCATS and a pig-oriented collaboration with partners in China.
Once activated by cancer immunotherapy drugs, T cells still need fuel (CD28)
— Rafi Ahmed’s lab at Emory Vaccine Center. Also see T cell revival predicts lung cancer outcomes. At Thursday’s Winship symposium on cancer immunotherapy, Rafi said the name of the game is now combinations, with an especially good one being PD-1 inhibitors plus IL2.
Pilot study shows direct amygdala stimulation can enhance human memory
— Cory Inman, Joe Manns, Jon Willie. Effects being optimized, see SFN abstract.
Immune responses of five returning travelers infected by Zika virus
— Lilin Lai, Mark Mulligan. Covered here, Emory Hope Clinic and Baylor have data from more patients.
Frog slime kills flu virus
— Joshy Jacob’s lab at Emory Vaccine Center. A follow-up peptide with a name referencing Star Wars is coming.
In lung cancer patients who were taking immunotherapy drugs, testing for revived immune cells in their blood partially predicted whether their tumors would shrink. The results were published online by PNAS on April 26.
This finding comes from a small study of 29 patients, who were being treated at Winship Cancer Institute of Emory University with drugs blocking the PD-1 pathway, also known as checkpoint inhibitors.
The study supports a straightforward idea: if tumor-specific CD8 T cells appear to respond to the drug (nivolumab, pembrolizumab or atezolizumab), that’s a good sign. This avenue of investigation may also help researchers figure out why some patients do not benefit from checkpoint inhibitor drugs, and how to combine those drugs with other treatments to increase response rates.
While looking for activated immune cells in the blood is not yet predictive enough for routine clinical use, such tests could provide timely information. Monitoring the immune response could potentially help oncologists and patients decide, within just a few weeks of starting immunotherapy drugs, whether to continue with the treatment or combine it with something else, says co-senior author Suresh Ramalingam, MD, Winship’s deputy director.
“We hypothesize that re-activated CD8 T cells first proliferate in the lymph nodes, then transition through the blood and migrate to the inflamed tissue,” says Rafi Ahmed, PhD, director of the Vaccine Center and a Georgia Research Alliance Eminent Scholar. “We believe some of the activated T cells in patients’ blood may be on their way to the tumor.”
The rest of the Emory Vaccine Center/Winship Cancer Institute press release is here. A few additional points: Read more
Cancer immunotherapy drugs blocking the PD-1 pathway – known as checkpoint inhibitors – are now FDA-approved for melanoma, lung cancer and several other types of cancer. These drugs are often described as “releasing the brakes” on dysfunctional T cells.
A new study from Emory Vaccine Center and Winship Cancer Institute researchers shows that even if the PD-1-imposed brakes are released, the tumor-specific T cells still need “fuel” to expand in numbers and restore effective immune responses. That fuel comes from co-stimulation through a molecule called CD28.
The results were published Thursday by the journal Science.
Despite the success of PD-1-targeting drugs, many patients’ tumors do not respond to them. The study’s findings indicate that CD28’s presence on T cells could be a clinical biomarker capable of predicting whether drugs targeting PD-1 will be effective. In addition, the requirement for CD28 suggests that co-stimulation may be missing for some patients, which could guide the design of combination therapies.
For the rest of our press release and quotes from authors Rafi Ahmed, Alice Kamphorst and Suresh Ramalingam, please go here. For some additional links and thoughts on PD-1 and CD28, read on:
It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After divertingÂ some of these topics into the 2015 crystal ball
,Â I corralledÂ them into themes.
1. Cardiac cell therapy
2. Mobilizing the body’s own regenerative potential
4. Parkinson’s disease therapeutic strategies
(Gary Miller, better packaging for dopamine could avoidÂ stress to neurons).
5. Personal genomics/exome sequencing
, likeÂ Emory’s Robert Gross
and Costas Hadjpanayis, do amazing things
7. Fun vsÂ no fun
Our Web expert
tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
In Greek mythology, the chimera was a monstrous fire-breathing creature composed of the parts of three animals: a lion, a snake and a goat.
Adoptive cell transfer is advancing as a cancer immunotherapy technique. It involves removing some of a patientâ€™s immune cells, culturing them in the laboratory, and then infusing the cells back into the patient. The idea is to enhance the ability of the immune cells to attack the tumors far beyond what the immune system was able of doing on its own.
Two promising examples are the National Cancer Instituteâ€™s approach of treating advanced melanoma with IL-2-stimulated immune cells, and several investigatorsâ€™ approach of genetically engineering T cells to attack leukemias or lymphomas.
Jacques Galipeau and colleagues at Winship Cancer Institute have developed a chimeric molecule for stimulating immune cells, which appears to have unique powers beyond simply the sum of its two parts. The molecule is called GIFT4, a fusion of the immune signaling molecules GM-CSF (often used in cancer treatment) and IL-4.