İki gruptan oluşan araştırma ekibi çalışmalarında uzun süreli yaşayan bağışıklık hücrelerini oluşturarak özellikli HIV ve Kanser antijenlerine karşı direnç gösterip onları bozulmalarını sağlayacak bir yöntemi geçen günlerde Cell: Stem cell dergisinde iki makale halinde yayınladılar. Japonya’nın Kyoto Üniversitesinde HIV projesinde bulunan kök hücre biyologu Dr. Shin Kaneko; yaptıkları bu çalışma ile laboratuar koşullarında kronik rahatsızlıkların antijenlerine özgün sınırsız sayıda olgun cytotoxic T hücrelerini (Bağışıklık hücresi çeşitlerinden biri) üretip canlandırabildiklerini belirtiyor.
Şu ana kadar T hücreleri üzerindeki en büyük problem vücutta uyuşuk olarak bulunanların uzun süre yaşamını sürdürürken; aktif olarak bulunanlar ise zamanla etkinliğini ve çoğalma yeteneklerini kaybettiği hücre yaşlanması sürecine giriyor olmasıydı. Bu da hastalıklar ile mücadelede önemli bir eksiklik oluşturuyordu. Pensilvalya Üniversitesinden immünolog Dr. Carl June; yaşlı hücrelerin yeniden çoğalacak olgunluğa dönüşmesinin hücre terapileri için çok kritik bir konu olduğunu belirtiyor.
Yapılan çalışmada araştırmacılar, HIV’li ve melignant melonama'lı (kanser türü) hastalardan yaşlanma sürecine girmiş T hücrelerini aldılar. Daha sonra bu hücrelerin yağışlılık süreci ile mücadele etmek amacı ile zararsız virüsler kullanarak eklenen 4 genle yaşlanma sürecindeki T hücreleri, 2012 Nobel fizyoloji ve tıp ödülünün sahibi Shinya Yamanaka’nın geliştirdiği induced pluriopotent stem cells’lerin (IPSC- Uyarılmış pluripotent kök hücreler) içine güdümlediler. Bu işlemler sonucunda olgun T hücrelerinin telomer uzunluklarını (biyolojik yaş belirleme birimleri) %30-50 oranında arttığı ve bu hücrelerin gençleşmesinin gerçekleştiği araştırmacılarca gözlendi. İşin heyecan veren kısmı ise tüm bu işlemler sonucunda T hücrelerinin HIV ve kanserli bölgelere olan spesifikliğinin halen sürdürüyor olmasıydı.
Bu sayede kan dolaşımında 10 ve 100 kat daha fazla aktif genç hücrenin oluşturulması sağlandı. Tokyo Üniversitesi Kök hücre terapisi bölümünden Dr. Hiromutsi Nakauchi, sonunda bir T hücre bankasına sahip olabileceklerini ve bu sayede farklı HIV epitoplarına karşı etkili bir tedavi umudunun doğduğunu belirtiyor.
Japonya’nın Yokohama kentinde bulunan RIKEN araştırma merkezinde alerji ve immunoloji üzerine çalışmalarını yürüten aynı zamanda bu projenin kanser ile ilgili bölümünde çalışan immunolog Dr. Hiroshi Kawamoto ise ileride uyarılmış kök hücreleri kanserli hastalara vererek daha fazla aktif T hücrelerinin oluşturulabileceğini ve kansere karşı daha uzun süreli etkili bir bağışıklık sağlanılabilineceğini düşünüyor.
Her iki grupta bu yöntemin farklı virüslerden kaynaklı hastalıklar ile farklı kanser türlerindeki etkisini de araştırmayı planlıyor.
Amerikan Ulusal Kanser Enstitüsü'nden Nicholas Restifo; yeniden programlanmış hücrelerin kanserli hücrelere dönüşme riskinin olduğunu ama kansere karşı immünolojik terapiler geliştirme adına bu hücrelerin kullanılmasının sorunların çözümü adına heyecan verici olduğunu belirtiyor.
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New techniques could improve reprogrammed-immune-cell treatment of HIV and cancer
03 Jan 2013 | 15:50 EST | Posted by Kevin Jiang | Category: AIDS, Cancer, Stem cells/cloning
Recent experiments exploring the use of patients’ own genetically reprogrammed immune cells toward the treatment of chronic diseases such as HIV and cancerhave had encouraging and sometimes high-profileresults. Yet, these studies have only been conducted in a limited number of individuals, and outcomes have been inconsistent, ranging from complete remission to complete inefficacy.
Now, two teams of researchers have demonstrated a method of using patients’ cells to create long-lived immune cells that target specific HIV and cancer antigens, and appear to resist degradation over time. Their work was published today in two separate papers in Cell Stem Cell.
“Our method has realized the functional rejuvenation and unlimited production of mature cytotoxic T cells with desired antigen-specificity for the first time in vitro,” says Shin Kaneko a stem cell biologist at Kyoto University in Japan and a co-author of the HIV-related study.
Difficulties in previous attempts to extract and reengineer T cells from patients are thought to be due in partto a phenomenon known as ‘cellular senescence’, a type of aging process. Naïve, quiescent T cells can survive for decades in the body. But active T cells, particularly those expanded outside the body in the laboratory, can gradually lose the ability to proliferate and be effective. This can lead to insufficient numbers of active immune cells to combat disease.
“Replicative senescence is likely to be a major issue for adoptive cell therapy,” says Carl June, an immunologist at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. “[These papers] address this issue and are exciting demonstrations of the progress in cell and developmental biology.”
The first part for both teams was to extract T cells—one group from an HIV-infected individual and the other group from a person with malignant melanoma—that already could detect the respective diseases. To combat senescence they then guided those cells into an induced pluripotent stem cell-state by exposing them to a harmless virus that introduced four genes in a process developed by last year’s Nobel Prize winner in medicine and physiology, Shinya Yamanaka. After coaxing the induced cells to mature back into T cells, the researchers found that these new cells were characterized by 30 to 50% longer telomere caps on the ends of their chromosomes, leading to longer life spans when grown in a lab dish. Notably, after this manipulation, the cells could still specifically target HIV and melanoma.
Additionally, they demonstrated a 10- to 100-fold increase in the cells’ ability to multiply, a potential solution to insufficient numbers of circulating immune cells. “Eventually, we will accumulate [banks of T cells] against various epitopes of HIV that would allow us to develop a more effective, hopefully curative therapy,” saysHiromitsu Nakauchi, director of the Stem Cell Therapy division at the University of Tokyo and senior author on the HIV study.
Hiroshi Kawamoto, an immunologist at the RIKEN Research Center for Allergy and Immunology in Yokohama, Japan and senior author of the melanoma study, believes it could be possible to transfer induced stem cells back to cancer patients in the future. Directed into the thymus, they could give rise to a constantly replenishing population of mature T cells. “If such [a] patient is appropriately immunized [with the T cells], we can expect long-lasting immunity against cancer,” he says.
Both groups plan to test their souped-up T cells in animal models to study safety and efficacy, as well as exploring other potential components of the virus or cancers the cells might target.
Nicholas Restifo, an immunologist at the US National Cancer Institute in Bethesda, Maryland, cautions that reprogrammed cells may possibility have the ability to become cancerous, so “eventual clinical usage must be very judicious.” However, he’s still a proponent of the therapeutic approach: “This ‘reincarnation’ of T cells for immunotherapy is an exciting idea.”
New techniques could improve reprogrammed-immune-cell treatment of HIV and cancer
03 Jan 2013 | 15:50 EST | Posted by Kevin Jiang | Category: AIDS, Cancer, Stem cells/cloning
Recent experiments exploring the use of patients’ own genetically reprogrammed immune cells toward the treatment of chronic diseases such as HIV and cancerhave had encouraging and sometimes high-profileresults. Yet, these studies have only been conducted in a limited number of individuals, and outcomes have been inconsistent, ranging from complete remission to complete inefficacy.
Now, two teams of researchers have demonstrated a method of using patients’ cells to create long-lived immune cells that target specific HIV and cancer antigens, and appear to resist degradation over time. Their work was published today in two separate papers in Cell Stem Cell.
“Our method has realized the functional rejuvenation and unlimited production of mature cytotoxic T cells with desired antigen-specificity for the first time in vitro,” says Shin Kaneko a stem cell biologist at Kyoto University in Japan and a co-author of the HIV-related study.
Difficulties in previous attempts to extract and reengineer T cells from patients are thought to be due in partto a phenomenon known as ‘cellular senescence’, a type of aging process. Naïve, quiescent T cells can survive for decades in the body. But active T cells, particularly those expanded outside the body in the laboratory, can gradually lose the ability to proliferate and be effective. This can lead to insufficient numbers of active immune cells to combat disease.
“Replicative senescence is likely to be a major issue for adoptive cell therapy,” says Carl June, an immunologist at the University of Pennsylvania’s Perelman School of Medicine in Philadelphia. “[These papers] address this issue and are exciting demonstrations of the progress in cell and developmental biology.”
The first part for both teams was to extract T cells—one group from an HIV-infected individual and the other group from a person with malignant melanoma—that already could detect the respective diseases. To combat senescence they then guided those cells into an induced pluripotent stem cell-state by exposing them to a harmless virus that introduced four genes in a process developed by last year’s Nobel Prize winner in medicine and physiology, Shinya Yamanaka. After coaxing the induced cells to mature back into T cells, the researchers found that these new cells were characterized by 30 to 50% longer telomere caps on the ends of their chromosomes, leading to longer life spans when grown in a lab dish. Notably, after this manipulation, the cells could still specifically target HIV and melanoma.
Additionally, they demonstrated a 10- to 100-fold increase in the cells’ ability to multiply, a potential solution to insufficient numbers of circulating immune cells. “Eventually, we will accumulate [banks of T cells] against various epitopes of HIV that would allow us to develop a more effective, hopefully curative therapy,” saysHiromitsu Nakauchi, director of the Stem Cell Therapy division at the University of Tokyo and senior author on the HIV study.
Hiroshi Kawamoto, an immunologist at the RIKEN Research Center for Allergy and Immunology in Yokohama, Japan and senior author of the melanoma study, believes it could be possible to transfer induced stem cells back to cancer patients in the future. Directed into the thymus, they could give rise to a constantly replenishing population of mature T cells. “If such [a] patient is appropriately immunized [with the T cells], we can expect long-lasting immunity against cancer,” he says.
Both groups plan to test their souped-up T cells in animal models to study safety and efficacy, as well as exploring other potential components of the virus or cancers the cells might target.
Nicholas Restifo, an immunologist at the US National Cancer Institute in Bethesda, Maryland, cautions that reprogrammed cells may possibility have the ability to become cancerous, so “eventual clinical usage must be very judicious.” However, he’s still a proponent of the therapeutic approach: “This ‘reincarnation’ of T cells for immunotherapy is an exciting idea.”
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