분자유전학실험실 (단국대학교 분자생물학과)



 이성욱 ( 2016-07-19 16:50:01 , Hit : 867
 Revisiting CAR T-Cells for Treating HIV Shows Promise

GEN News Highlights

Jul 18, 2016

The rise in the development of chimeric antigen receptor (CAR) T cells for use against various forms of cancer has been well documented due to encouraging results in recent years. Yet, the earliest CAR T-cell trials were done in the early 1990s for HIV-1 infections but were sidelined due to less than efficacious results. However, many scientists believe that the emerging number of broadly neutralizing antibodies (bnAbs) could provide real opportunities to reconsider CAR T cells as a viable approach for HIV immunotherapy.

Now, investigators from the UCLA AIDS Institute and Center for AIDS Research have reported on their recent results surrounding the discovery of potent antibodies that can be used to generate CAR T cells that kill HIV-1–infected cells.

CARs are genetically engineered immune T cells that produce receptors on their surface designed to target and kill specific cells containing viruses or tumor proteins. Chimeric receptors are the focus of ongoing research into how gene immunotherapy can be used to fight cancer. However, they could also be used to create a strong immune response against HIV.

Interestingly, the human immune system does initially respond to and attack HIV, although it quickly becomes overwhelmed due to the rapid viral replication and ability to sequester itself within immune cells to avoid further elimination—destroying the immune system and leaving the body vulnerable to a host of infections and diseases. Over the years researchers have been looking for ways to strengthen the immune system against HIV, and it now appears CARs could be a viable weapon in that fight.      

"We took new generation antibodies and engineered them as artificial T-cell receptors, to reprogram killer T cells to kill HIV-infected cells," explained senior study author Otto Yang, M.D., professor of medicine in the division of infectious diseases at the David Geffen School of Medicine at UCLA and director of vaccine and pathogenesis research at the AIDS Institute and Center for AIDS Research. "what works in a test tube doesn't necessarily work in a person, so the next step is to find strategies to put these receptors into humans. But this therapy shows enough promise to move forward with further research."

The findings from this study were published recently in the Journal of Virology in an article entitled “HIV-1-Specific Chimeric Antigen Receptors Based on Broadly-Neutralizing Antibodies.”

The UCLA team utilized seven recently discovered bnAbs that have the ability to bind multiple strains of invading viruses, unlike earlier isolated antibodies that tend to bind few strains. These antibodies were re-engineered as artificial CAR T-cell receptors to have activity against broad strains of HIV.

“We used sequences from seven well-defined bnAbs varying in binding sites and generated single chain-antibody-based CARs,” the authors wrote. “These included 10E8, 3BNC117, PG9, PGT126, PGT128, VRC01, and X5. Each novel CAR exhibited conformationally relevant expression on the surface of transduced cells, mediated specific proliferation and killing in response to HIV-1-infected cells, and conferred potent antiviral activity (reduction of viral replication in log10 units) to transduced CD8+ T lymphocytes.”

While the receptor approach has been in use for almost 10 years to fight cancer, this is the first attempt in 15 years to use the technique to treat HIV, when initial studies proved ineffective.

The researchers were excited by their findings stating that the "antiviral activity [of these CARs] was reproducible but varied according to the strain of virus. These findings indicated that bnAbs are excellent candidates for developing novel CARs to consider for the immunotherapeutic treatment of HIV-1.”

However, Dr. Yang did urge caution in over-interpretation of the results, noting that "what works in a test tube doesn't necessarily work in a person, so the next step is to find strategies to put these receptors into humans. But this therapy shows enough promise to move forward with further research.”







1207   Outsourcing Gene Editing to the Public-Online Game Challenges Players to Design CRISPR On/Off Switch  이성욱 2017/09/05 804
1206   Resistance to HIV Engineered Via CRISPR  이성욱 2017/08/07 813
1205   Cancer Onset May Be Caused by Immune System Fighting Viruses  이성욱 2017/08/25 813
1204   Uncovering Functions of Circular RNAs  이성욱 2017/08/14 817
1203   [바이오토픽] 드디어 올 것이 왔다: CRISPR, 생존가능 인간배아의 질병초래 유전자 교정 성공  이성욱 2017/08/03 821
1202   Zika Update  이성욱 2016/03/15 824
1201   CRISPR Corrects RNA-based Disease Defects  이성욱 2017/08/14 828
1200   “유전자 치료 법률 금지 한국 유일” vs “생명체 설계도 바꾸는 건 문제”  이성욱 2017/08/28 831
1199   CRISPR Fixes Stem Cells Harboring Blindness-Causing Defect  이성욱 2016/02/01 842
1198   First In Vivo Human Genome Editing to Be Tested in New Clinical Trial  이성욱 2017/05/18 850
1197   유전자치료제 '인보사' 연골재생 입증못해도 허가받은 까닭  이성욱 2017/07/14 859
1196   [바이오토픽] FDA 자문위원회, CAR-T(chimeric antigen receptor T cell) 승인 만장일치로 권고  이성욱 2017/07/14 859
1195   First In Vivo Function Found for Animal Circular RNA  이성욱 2017/08/14 861
1194   ‘단세포 인공생명체’ 눈앞에 성큼  이성욱 2017/03/11 863
  Revisiting CAR T-Cells for Treating HIV Shows Promise  이성욱 2016/07/19 867
1192   Engineered Human Liver Tissue Grows in Mice  이성욱 2017/07/25 872
1191   Using Gene Editing to Delete HIV from Human T Cells  이성욱 2016/03/23 873
1190   CRISPR Can Tag RNA  이성욱 2016/03/26 875
1189   유전자 가위로 바이러스 제거한 '청정 돼지' 나왔다  이성욱 2017/08/24 877
1188   독감바이러스의 ‘RNA 도둑질’  이성욱 2017/05/08 879

[1][2][3] 4 [5][6][7][8][9][10]..[64] [다음 10개]
 

Copyright 1999-2023 Zeroboard / skin by ROBIN