Welcome, Guest. Please login or register.
November 19, 2017, 09:32:58 AM

Login with username, password and session length

  • Total Posts: 722449
  • Total Topics: 58706
  • Online Today: 311
  • Online Ever: 1421
  • (August 13, 2016, 05:18:44 AM)
Users Online


Welcome to the POZ Community Forums, a round-the-clock discussion area for people with HIV/AIDS, their friends/family/caregivers, and others concerned about HIV/AIDS.  Click on the links below to browse our various forums; scroll down for a glance at the most recent posts; or join in the conversation yourself by registering on the left side of this page.

Privacy Warning:  Please realize that these forums are open to all, and are fully searchable via Google and other search engines. If you are HIV positive and disclose this in our forums, then it is almost the same thing as telling the whole world (or at least the World Wide Web). If this concerns you, then do not use a username or avatar that are self-identifying in any way. We do not allow the deletion of anything you post in these forums, so think before you post.

  • The information shared in these forums, by moderators and members, is designed to complement, not replace, the relationship between an individual and his/her own physician.

  • All members of these forums are, by default, not considered to be licensed medical providers. If otherwise, users must clearly define themselves as such.

  • Forums members must behave at all times with respect and honesty. Posting guidelines, including time-out and banning policies, have been established by the moderators of these forums. Click here for “Am I Infected?” posting guidelines. Click here for posting guidelines pertaining to all other POZ community forums.

  • We ask all forums members to provide references for health/medical/scientific information they provide, when it is not a personal experience being discussed. Please provide hyperlinks with full URLs or full citations of published works not available via the Internet. Additionally, all forums members must post information which are true and correct to their knowledge.

  • Product advertisement—including links; banners; editorial content; and clinical trial, study or survey participation—is strictly prohibited by forums members unless permission has been secured from POZ.

To change forums navigation language settings, click here (members only), Register now

Para cambiar sus preferencias de los foros en español, haz clic aquí (sólo miembros), Regístrate ahora

Finished Reading This? You can collapse this or any other box on this page by clicking the symbol in each box.

Author Topic: HIV-Killing Stem Cell Paper Glosses Over Key Caveat  (Read 1404 times)

0 Members and 1 Guest are viewing this topic.

Offline younghopefulpoz

  • Member
  • Posts: 55
HIV-Killing Stem Cell Paper Glosses Over Key Caveat
« on: April 29, 2012, 06:38:15 AM »
HIV-Killing Stem Cell Paper Glosses Over Key Caveat
By Richard Jefferys
From Treatment Action Group
April 20, 2012
A recent paper describing the engineering of stem cells to generate HIV-specific CD8 T cells has drawn considerable media attention and, regrettably but not untypically, many of the stories are profoundly misleading. Examples of headlines include:
"Scientists engineer stem cells which suppress HIV: cure for AIDS possible"
"New breakthrough shows stem cells can be engineered to fight HIV!?"
"UCLA-engineered stem cells seek out and kill HIV in living organisms"
The last example is the headline of the UCLA press release that accompanied publication of the paper in PLoS Pathogens. It is not inaccurate, but what is likely not apparent to many people is that just about everyone's stem cells make CD8 T cells with HIV-specific T cell receptors (TCRs) that would have similar potential to suppress HIV replication in humanized mice (the model used in the study). My stem cells have probably made some while I'm writing this post and the same is true for anyone reading it. Although some TCRs appear particularly adept at recognizing HIV antigens, it is not the lack of HIV-specific CD8 T cells with appropriate TCRs that underlies the inability to control HIV replication in most people; rather, the preponderance of evidence indicates that the functionality of the HIV-specific CD8 T cell response is severely compromised.
The PLoS Pathogens paper does discuss some of the potential reasons for this lack of CD8 T cell function, but omits any direct reference to the one most researchers consider crucial: the lack of functional HIV-specific CD4 T cell help. Over the last couple of decades it has become clear that the generation and maintenance of effective CD8 T cell responses is almost always dependent on help from CD4 T cells (and it is uncertain if the rare descriptions of CD4-independent CD8 T cell responses are relevant to people, or reflect the artificiality of the specific model systems used). HIV-specific CD4 T cells have been show to be preferential targets for HIV infection, and these responses are weak and dysfunctional in the vast majority of HIV-positive people (with the notable exception of many elite controllers). The UCLA approach to generating HIV-specific CD8 T cells via stem cell modification may represent a technical achievement, but it has little prospect of being therapeutically useful if there is not also a strategy to address HIV-specific CD4 T cells. Used alone, the results would be expected to mirror those achieved in prior studies where HIV-specific CD8 T cells were infused directly into people with HIV; the cells trafficked to the sites of HIV replication, showed some transient activity, and then became as dysfunctional as the many HIV-specific CD8 T cells that were already present.
While this analysis may sound very pessimistic, there are approaches that might address the HIV-specific CD4 T cell part of the equation. The genetic modification of CD4 T cells to make them resistant to HIV infection by eliminating CCR5 expression -- an approach developed by Sangamo BioSciences and currently in clinical trials -- is an example. Carl June, one the trial investigators, has long-term plans to combine the Sangamo treatment with gene-modified HIV-specific CD8 T cells. At the moment the CD8 T cells are genetically altered in the lab and re-infused as opposed to introducing the modification via stem cells; a phase I trial is ongoing at the University of Pennsylvania. Because there is evidence that some CD8 T cell TCRs may work better than others, there might be potential benefits to combining HIV-resistant CD4 T cells and CD8 T cells with souped-up TCRs (as June ultimately plans to do). The UCLA technique of introducing TCRs by modifying stem cells has several advantages compared to manipulating the CD8 T cells directly, so it's not as if the study is without merit, it's just unfortunate that the near-term therapeutic implications of the work have been severely exaggerated in the media coverage.




Terms of Membership for these forums

© 2017 Smart + Strong. All Rights Reserved.   terms of use and your privacy
Smart + Strong® is a registered trademark of CDM Publishing, LLC.