Deciphering the Puzzle
A new round of amfAR’s Countdown to a Cure initiative grants support novel cure research
by Jeannie Wraight
amfAR has awarded a new round of grants, totaled at $3.5 million dollars, for its Countdown to a Cure for AIDS Initiative. The grants support research focused on reducing or eliminating persistent viral reservoirs. AmfAR’s Countdown to a Cure Initiative was created to streamline amfAR’s efforts to “find” a scientific basis for a cure for HIV by the end of 2020. Overall, amfAR plans to invest $100 million in this effort and has thus far awarded $42 million in grants to support the research of more than 220 scientists in ten countries.
In this most recent round of grants, thirteen awards were given in two categories. Six research teams were awarded a total of $2.3 million under the amfAR Research Consortium on HIV Eradication (ARCHE) and six “innovation” grants were awarded for a total of $1.2 million.
Whereas scientific research is often competitive, partially due to a limited number of funding opportunities, amfAR, through its Research Consortium on HIV Eradication, promotes collaboration among its recipients and seeks synergies among their successes.
Scott G. Kitchen, PhD, Associate Professor of Medicine and director of the UCLA Humanized Mouse Core Laboratory, Division of Hematology/Oncology at The David Geffen School of Medicine, received one of amfAR’s ARCHE grants to continue his lab’s research on a novel HIV gene therapy.
Dr. Kitchen’s research focuses on a chimeric antigen receptor, which is an artificial receptor on T cells that allows the cell to recognize HIV-infected cells and ultimately kill them. These artificial receptors redirect stem cells to allow for the development of a larger number of mature HIV-specific T cells that will more effectively attack HIV-infected cells. This would enable the immune system to naturally and perpetually produce these cells throughout a person’s lifetime, allowing the immune system to not only control HIV infection, but, Dr. Kitchen hypothesizes, to potentially eradicate HIV.
Dr. Kitchen’s lab has several chimeric antigen receptor candidates. The funds from amfAR’s Countdown to a Cure Initiative grant would allow for finding the best candidate to utilize as a therapeutic agent to begin clinical trials. This would be done similar to a bone marrow transplant, where a person’s stem cells are removed and reengineered to contain these receptors. They would then graft to a person’s bone marrow and form the HIV- specific T cells.
“The use of chimeric antigen receptors is a bit out of the box compared to current HIV strategies but it has been applied to peripheral T cells in treating various types of cancers. Companies like Juno and Kite Pharmaceuticals and others have had success and are conducting clinical trials in cancer. Ours is different in it is being applied to stem cells which has certain advantages such as the potential to promote lifelong immunity verses a more defined life span of immunity, as is now being seen in peripheral T cells in oncology. By providing a greater level of immunity, we’re hoping to provide a means of eradicating the virus,” stated Dr. Kitchen.
Dr. Brad Johnson PhD, from the University of Maryland in Baltimore is one of the six recipients of amfAR’s “innovation” grants. Dr. Johnson’s research focuses on the early stage development of a therapeutic utilizing a new class of broadly neutralizing antibodies that could be widely used in people with different viral strains. Dr. Johnson’s research is based on the work of Dr. Louis Picker’s lab, whose groundbreaking research saw success in achieving potent viral control of SIV with a unique vaccine, used in rhesus macaques (RM).
In Dr. Picker’s vaccine study, half of the twenty-four rhesus macaques who received a cytomegalovirus vector vaccine demonstrated long-term control of SIV-specific effector-memory T cells. Thirteen of the twenty-four RM who received a RhCMV vector vaccine or a RhCMV vector followed by a adenovirus 5 (Ad5) vector achieved early and complete control of SIV. In all but one of the thirteen, long-term protection of over one year was seen.
In Dr. Picker’s vaccine, killer T cells were able to recognize infected cells in an unconventional way. Cells naturally show, on their surface, an inventory of viral peptides of the proteins they are making. Dr. Jones described this as a window that enables killer T cells to see what cells are infected. According to Dr. Jones, with the Picker vaccine “a different set of windows was used that aren’t normally seen in a natural response to HIV. They are an unexploited target on the cell surface that even though not used by the immune system, they are always there [and not a result of the vaccine].” Dr. Jones’ lab will develop an antibody which will act as a “shortcut to creating this immune response” and allow killer T cells to see through this window, tell which cells are infected, and kill off these cells.
Dr. Jones’ research is milestone-based and, if successful, over a two- year period of time, will lead to the development of an antibody that could be studied as a therapeutic in humans.
AmfAR’s dedicated support of research such as that of Dr. Kitchen and Dr. Jones, as well as the other amfAR recipients, represents a concerted effort to systematically approach and decipher the complex puzzle of reducing or eliminating the HIV viral reservoirs that represent the greatest barrier to curing HIV infection.
Jeannie Wraight is the former editor-in-chief and co-founder of HIV and HCV Haven (www.hivhaven.com) and a blogger and writer for TheBody.com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in New York City.