In a previous post I mentioned that, in the case of leukaemia sufferers, scientists have discovered a new therapy which could remove the need for the risky, painful and expensive bone marrow transplant procedure. This would be done by harvesting T cells from the cancer patient, and genetically modifying them using disease-neutralised HIV cells. Well today, at the International AIDS Society Conference in Kuala Lumpur, it was announced that two men may have been cured of the HIV virus as a result of transplants for their leukaemia!
This is not the first time that a stem-cell transplant for a patient suffering from both HIV and leukaemia has effectively cured the patient of HIV. Timothy Brown, the famous “Berlin Patient”, was the first person to be cured of the disease in 2008[i]. But in Timothy’s case, the donor was one of the small proportion of the population which are immune to the virus. This immunity comes from the inherited genetic mutation which shortens the CCR5 gene. It is this gene that the HIV virus uses to enter the CD4+ T cells, and thus to infect the patient[ii].
In the cases of the two Boston Patients, both were recipients of stem-cells from CCR5+ (i.e. non-mutation) donors. This means that something else, rather than the HIV-1 resistant truncated CCR5 gene, was at work. It is possible that it is graft-versus-host disease - one of the very things that makes bone-marrow transplants so dangerous - that is the answer, as it could be responsible for wiping out the remaining HIV reservoir in the patients.[iii]
Currently, the two Boston Patients have stopped taking their antiretroviral drugs for 15 and 7 week respectively, and both currently show no sign of HIV in the blood[iv]. However, caution is being urged before stating that the men have been cured. It is unknown whether there is another reservoir of HIV in the body from which the virus could theoretically resurrect. It is possible that the brain, heart tissue or the gut could harbour latent HIV cells. In fact, it is known that it is through the proliferation of CCR5+ genes in the gut of newborn babies that HIV for a mother’s infected breast milk can facilitate the infection of the child[v].
Also, the bone-marrow transplant procedure itself is not without its dangers. It is also painful, and expensive. As a cure for HIV, it is not currently a viable option. But its importance lies in the fact that it has given scientists another piece of the puzzle in the fight to understand and cure this terrible disease. It has also given the world its possible third and fourth survivors of HIV[vi]. That at least is worth celebrating!
[i] “Stem-cell transplant seems to fend off HIV” 14 Nov 2008 Nature Blog.
[ii] “Long-Term Control of HIV by CCR5 Delta32/Delta32 Stem-Cell Transplantation” Gero Hütter, M.D., Daniel Nowak, M.D., Maximilian Mossner, B.S., Susanne Ganepola, M.D., Arne Müßig, M.D., Kristina Allers, Ph.D., Thomas Schneider, M.D., Ph.D., Jörg Hofmann, Ph.D., Claudia Kücherer, M.D., Olga Blau, M.D., Igor W. Blau, M.D., Wolf K. Hofmann, M.D., and Eckhard Thiel, M.D. N Engl J Med February 12, 2009; 360:692-698
[iii] “Stem-cell transplants may purge HIV” Erika Check Hayden, Nature News. 03 July 2013
[v] “Memory CD4+CCR5+ T cells are abundantly present in the gut of newborn infants to facilitate mother-to-child transmission of HIV-1” Madeleine J. Bunders, Chris M. van der Loos, Paul L. Klarenbeek, John L. van Hamme, Kees Boer, Jim C. H. Wilde, Niek de Vries, Rene A. W. van Lier, Neeltje Kootstra, Steven T. Pals3, and Taco W. Kuijpers. Blood. November 22, 2012 vol. 120 no. 22 4383-4390
[vi]The second being a baby in Mississippi born to a HIV positive mother, who started receiving antiretroviral treatment before she was 30 hours old. The treatment has so far removed all trace of the virus from her system. See: “Infant's vanquished HIV leaves doctors puzzled” Erika Check Hayden Nature. 05 March 2013
A ray of light has emerged in the global fight against cancer which presents some fascinating science, and shows just how far we have come in our ability to engineer our own cells to fight this deadly disease.
A current trending video (shown below) has highlighted an ongoing clinical trial that has been having some miraculous results. It focuses on the story of Emma, a girl who had seen her leukaemia return twice, and who was looking for some sliver of hope that would be nothing short of a miracle.
But the journey did not start with Emma. In 2010, Dr Carl H. June, of the Perelman School of Medicine at the University of Pennsylvania, enrolled a patient, who had for years been receiving various forms of treatment for chronic lymphoid leukaemia (CLL), in a clinical trial for a newly devised treatment for cancer.[i]
This treatment involved harvesting T-cells from the leukaemia sufferer, and modifying them to target and kill the cancerous cells in the body. This is done by using a viral agent to “infect” the T cells with new genetic information, effectively recoding them to attack Cancer cells.
The best viruses for the job are what are known as lentiviruses, one of which, the one that was used for this purpose, was the HIV virus. These viruses are adept at getting their own genetic code into host cells, and as such are the perfect vehicle for the modification of patient T cells.
The HIV virus was of course modified to prevent it from infecting the patient, and as such is not HIV as we know it, but a genetically modified version that still has viral qualities but which are not harmful to the patient. Thus a patient given this treatment does not have HIV.
The newly modified cell is known as a chimeric antigen receptor. “Chimeric antigen receptors have theoretical advantages over other T-cell–based therapies. They use the patient’s own cells, which avoids the risk of graft-versus-host disease. They can be created quickly, and the same chimeric antigen receptor can be used for multiple patients.”[ii]
Each cell can kill over 1000 tumour cells, and with the advances made in the field, the cells can now successfully both attack cancer cells and proliferate within the patient, something which the first generation CAR’s could not do, producing only “transient cell division”[iii].
With all this destruction going on in the body and the pile-up of dead tumour cells, there are inevitably potent side-effects to the treatment. These include fever, blood pressure difficulties, and a whole host of issues that can bring the patient close to death.
Ongoing research will hopefully reduce the severity of these symptoms, and answer questions such as “how many T cells should a patient be given” and “how many treatments are needed to ensure complete remission”? Also, like the original bone marrow transplant option, this treatment would need to be a worldwide option, not just in a few “boutique cancer clinics”.[iv]
Still, Emma’s example, and those of the other cancer sufferers who have survived as a result of this new cutting edge treatment, should give us all new hope for the future in the fight against Cancer.
Check out the moving video below for Emma’s story.
[i] “Chimeric Antigen Receptor–Modified T Cells in Chronic Lymphoid Leukemia”. David L. Porter, M.D., Bruce L. Levine, Ph.D., Michael Kalos, Ph.D., Adam Bagg, M.D., and Carl H. June, M.D. N Engl J Med August 25, 2011 365 pp 725-733
[ii] “Redirecting T Cells” Walter J. Urba, M.D., Ph.D., and Dan L. Longo, M.D. N Engl J Med August 25, 2011 365;8 pp 754-7
[iv] “New Therapy Unleashes 'Serial Killer' Cells in Leukemia” Interview With Carl H. June, MD by Alice Goodman, Medscape News Today May 14, 2013