Edited genome donor cells have proven effective in fighting leukemia
Welcome to the iCover Blog Pages . The beginning of November 2015 was marked by an event that attracted the attention of many oncologists and genetic engineers of the planet. Sustainable remission in the treatment of cancer in humans has been achieved through the use of donor immune T cells with an edited genome. And the first patient to experience the possibilities of the proposed method was a one-year-old girl from the UK who suffered from one of the most aggressive types of cancer - acute lymphoblastic leukemia. We will talk about the method, treatment of Leila Richards and the results achieved in our publication.
Acute Lymphoblastic Leukemia was diagnosed by discouraging parents and was delivered by Layla Richards at 14 weeks old at Great Ormod Street Hospital ( GOSH)., Great Ormond Street Hospital), where the girl fell into a state of severe complication. According to the results of the examination and for further treatment, Leila was transferred to the Elephant Ward in Sheffield for cancer and leukemia patients . Several courses of chemotherapy, bone marrow transplantation, and all further attempts to take the situation under control and reverse the disease undertaken in the department did not bring the expected result. Seven weeks after a bone marrow transplant, another examination destroyed the hopes of Leila, Lisa and Ashley Richards' parents - the cancer returned.
GOSH doctors told their parents that they were exhausted and advised them to prepare for the worst. As the only possible alternative, they proposed an experimental method that had previously been tested only on laboratory mice. Not seeing a way out of a difficult situation, parents were forced to agree. “Our Leila was very bad and constantly experienced severe pain. The doctors could not give us any guarantees that the treatment would be effective. But it was impossible to look at it, and we agreed to use the new method, ”Ashley Richards shared his impressions.
The molecular scissor technology proposed for treating the girl was created by a joint team of specialists at the London Hospital GOSH and the Institute of Child Health (ICH, Institute of Chaild Healrh), jointly developing drugs for extremely rare childhood diseases. At the beginning of treatment, according to GOSH experts, the proposed method using modified donor T cells created in the laboratory of the hospital did not have clinical confirmation of the effectiveness of human use.
The essence of the method is to obtain T-type leukocytes from a healthy donor and then edit their genome in accordance with the “find and destroy” program for malignant leukemia cells. Cells - “hunters” created in the laboratory were called UCART 19.
Since the own resources of healthy T cells in people suffering from leukemia and who have undergone several chemotherapy courses (as in Leila's case) are not enough for the method used, the GOSH team proposes to use donor immune T cells that have undergone preliminary gene modification.
The action of molecular tools (TALEN®) can be compared to the action of precision scissors. Correction of T cell genes was carried out in such a way that:
Modified T cells of healthy donors obtained by the combined team of GOSH, ICH, University College London and the biotechnology company Cellectis in the amount of 1 bottle were originally intended for the final testing of the technology at the preclinical testing stage. The news of the situation in the Richards family forced specialists to reconsider their decision and provide the opportunity to use material and technology for experimental treatment. "Since the treatment was experimental, we should have received special permission, but in this situation and taking into account the consent of the child’s parents, there were no problems at this stage." Says Waseem Qasim, a GOSH immunologist, professor of cell and gene therapy at the Institute of Chaild Healrh.
UCART 19 cells in an amount of 1 ml were delivered to Leila by a single intravenous injection for 10 minutes. After the injection, in order to ensure reliable protection of the weakened immune system from potentially dangerous infections from the outside, the child spent some time in the strictest isolation.
The immune response in the form of a rash or fever, outwardly confirming the fact that the treatment works, doctors expected to receive within one to two weeks. However, after two weeks, external markers did not let themselves know. The result appeared a bit later in the form of a rash, while the condition of the girl throughout the entire quarantine period remained stable.
Thus, a few weeks after the injection of UCART 19 into Leila's body, the doctors recorded the fact of remission of the disease and concluded that the child has embarked on a path to complete recovery.
“Since the technology involves the use of specific donor immune T-cells of UCART 19 that have not been clinically tested, the effectiveness and safety of its use caused us reasonable doubts,” says Professor Paul Weiss (director of the bone marrow transplantation department of GOSH and the girl’s main doctor). The situation was complicated by the fact that "... Leila's leukemia was extremely aggressive. The result achieved in such a short time can be called almost a miracle." He adds.
After the doctors received confirmation that Leila did not have leukemia cells, two months after discharge from GOSH, the girl was given a bone marrow transplant, which allowed her to “renew” her blood and immune systems, which were injured by the disease and chemotherapy. Today, Leila was discharged from GOSH, stays at home, and regular ongoing examinations at this stage allow us to conclude that the bone marrow is healthy and the circulatory system is normal.
“Of course, leukemia is not chickenpox, it is a kind of“ constant ”that will always sit firmly in the back of our brains and cause doubts,” Ashley rightly believes, so it’s too early to relax, regular tests are ahead. “I believe that we are very lucky that we were in the right place at the right time to get a bottle of these cells.” - Lisa shares her impressions.
Leila and her family after discharge from GOSH hospital
Despite the results achieved, the authors themselves so far refrain from making loud statements, because "... The method we proposed has proved its effectiveness in only one case and requires statistical confirmation. ... We used the development in the treatment of girls with a very strong body and are not yet ready to claim that the technology is universal and equally outstanding results can be achieved in the treatment of all children, ”Vasim Kasim expressed his thoughts. “At the same time, the possibilities of genetic engineering methods using donor modified UCART 19 cells, demonstrated during the treatment of Leyla Richards, look simply stunning. And if you can get statistical confirmation of the effectiveness of proven technology in the treatment of other children,
The French biotechnology company Cellectis considered the possibility of expanded funding for a program that will test / confirm the clinical effectiveness of the UCART 19 development in large groups of patients. The first stage of the survey is scheduled for early 2016.
“A series of clinical trials of the first genetic edition of UCART is already on the horizon. Their successful completion could mark the beginning of a revolution in cancer immunotherapy.” Said Dr. Andre Chowlik, part-time CEO of Cellectis.
Note that genetically modified human cells have been used to treat cancer earlier, and work in this direction has been ongoing since a quarter century. So several adult patients were cured of leukemia in 2013. A vivid example is the case of 8-year-old Emily Whitehead from Philipsburg, suffering from lymphoblastic leukemia and becoming the first child at the University of Pennsylvania clinic who took part in the 2011 new gene drug testing program. The treatment was successful, after 2 years no signs of cancer were found in the girl. “It's amazing, you can take cells from a patient and make them into cells that attack a tumor,” said Dr. Janice Abkovitz, head of the Department of Blood Diseases at Washington University.
Emily Whitehead
In the described studies, the patient’s own cells were used as the “starting material”, in which a special gene was inserted, the purpose of which is to fight cancer cells. In the case of Leila, the number of healthy immune cells that could cope with the above task was not enough. Therefore, it was decided to use modified T cells of a healthy donor.
Today, clinical trials of gene therapy are being conducted in the case of some forms of congenital blindness, muscular dystrophy, hemophilia, and some promising approaches to blocking and treating HIV are being considered. And, according to experts, the victory over these serious ailments will be achieved first of all precisely by genetic modeling methods. In the future, the possibility of creating a set of populations of specific immune cells that are programmed to combat a particular type of infectious agent or cancer is being considered. This will mean that after making an accurate diagnosis to cure the patient it will be enough to introduce the corresponding modified cells into the blood. Having multiplied in the body, they will not only cope with the disease, but will also create effective protection against repeated illness of the same disease in the future.
Well, we wish a speedy amendment to Leila Richards and recovery to hundreds of thousands of cancer patients, for whom hope always dies last. And let the latest technologies help them in the very near future.
GOSH Hospital Learn
more about Leila Richards history and method on the Great Ormond Street Hospital official website . We invite our experts to share their views on the prospects of technology proposed by a joint group of researchers.
*****
Dear readers, we are always happy to meet and wait for you on the pages of our blog. We are ready to continue to share with you the latest news, review articles and other publications and will try to do our best to make the time spent with us useful for you. And, of course, do not forget to subscribe to our columns .
Our other articles and events
Acute Lymphoblastic Leukemia was diagnosed by discouraging parents and was delivered by Layla Richards at 14 weeks old at Great Ormod Street Hospital ( GOSH)., Great Ormond Street Hospital), where the girl fell into a state of severe complication. According to the results of the examination and for further treatment, Leila was transferred to the Elephant Ward in Sheffield for cancer and leukemia patients . Several courses of chemotherapy, bone marrow transplantation, and all further attempts to take the situation under control and reverse the disease undertaken in the department did not bring the expected result. Seven weeks after a bone marrow transplant, another examination destroyed the hopes of Leila, Lisa and Ashley Richards' parents - the cancer returned.
GOSH doctors told their parents that they were exhausted and advised them to prepare for the worst. As the only possible alternative, they proposed an experimental method that had previously been tested only on laboratory mice. Not seeing a way out of a difficult situation, parents were forced to agree. “Our Leila was very bad and constantly experienced severe pain. The doctors could not give us any guarantees that the treatment would be effective. But it was impossible to look at it, and we agreed to use the new method, ”Ashley Richards shared his impressions.
Method
The molecular scissor technology proposed for treating the girl was created by a joint team of specialists at the London Hospital GOSH and the Institute of Child Health (ICH, Institute of Chaild Healrh), jointly developing drugs for extremely rare childhood diseases. At the beginning of treatment, according to GOSH experts, the proposed method using modified donor T cells created in the laboratory of the hospital did not have clinical confirmation of the effectiveness of human use.
The essence of the method is to obtain T-type leukocytes from a healthy donor and then edit their genome in accordance with the “find and destroy” program for malignant leukemia cells. Cells - “hunters” created in the laboratory were called UCART 19.
Since the own resources of healthy T cells in people suffering from leukemia and who have undergone several chemotherapy courses (as in Leila's case) are not enough for the method used, the GOSH team proposes to use donor immune T cells that have undergone preliminary gene modification.
The action of molecular tools (TALEN®) can be compared to the action of precision scissors. Correction of T cell genes was carried out in such a way that:
- Ensure their immunity from antileukemic drugs accumulated in the body.
- Program them to detect and destroy leukemia cells.
Modified T cells of healthy donors obtained by the combined team of GOSH, ICH, University College London and the biotechnology company Cellectis in the amount of 1 bottle were originally intended for the final testing of the technology at the preclinical testing stage. The news of the situation in the Richards family forced specialists to reconsider their decision and provide the opportunity to use material and technology for experimental treatment. "Since the treatment was experimental, we should have received special permission, but in this situation and taking into account the consent of the child’s parents, there were no problems at this stage." Says Waseem Qasim, a GOSH immunologist, professor of cell and gene therapy at the Institute of Chaild Healrh.
UCART 19 cells in an amount of 1 ml were delivered to Leila by a single intravenous injection for 10 minutes. After the injection, in order to ensure reliable protection of the weakened immune system from potentially dangerous infections from the outside, the child spent some time in the strictest isolation.
Result
The immune response in the form of a rash or fever, outwardly confirming the fact that the treatment works, doctors expected to receive within one to two weeks. However, after two weeks, external markers did not let themselves know. The result appeared a bit later in the form of a rash, while the condition of the girl throughout the entire quarantine period remained stable.
Thus, a few weeks after the injection of UCART 19 into Leila's body, the doctors recorded the fact of remission of the disease and concluded that the child has embarked on a path to complete recovery.
“Since the technology involves the use of specific donor immune T-cells of UCART 19 that have not been clinically tested, the effectiveness and safety of its use caused us reasonable doubts,” says Professor Paul Weiss (director of the bone marrow transplantation department of GOSH and the girl’s main doctor). The situation was complicated by the fact that "... Leila's leukemia was extremely aggressive. The result achieved in such a short time can be called almost a miracle." He adds.
After the doctors received confirmation that Leila did not have leukemia cells, two months after discharge from GOSH, the girl was given a bone marrow transplant, which allowed her to “renew” her blood and immune systems, which were injured by the disease and chemotherapy. Today, Leila was discharged from GOSH, stays at home, and regular ongoing examinations at this stage allow us to conclude that the bone marrow is healthy and the circulatory system is normal.
“Of course, leukemia is not chickenpox, it is a kind of“ constant ”that will always sit firmly in the back of our brains and cause doubts,” Ashley rightly believes, so it’s too early to relax, regular tests are ahead. “I believe that we are very lucky that we were in the right place at the right time to get a bottle of these cells.” - Lisa shares her impressions.
Leila and her family after discharge from GOSH hospital
Expert Conclusions
Despite the results achieved, the authors themselves so far refrain from making loud statements, because "... The method we proposed has proved its effectiveness in only one case and requires statistical confirmation. ... We used the development in the treatment of girls with a very strong body and are not yet ready to claim that the technology is universal and equally outstanding results can be achieved in the treatment of all children, ”Vasim Kasim expressed his thoughts. “At the same time, the possibilities of genetic engineering methods using donor modified UCART 19 cells, demonstrated during the treatment of Leyla Richards, look simply stunning. And if you can get statistical confirmation of the effectiveness of proven technology in the treatment of other children,
Short term
The French biotechnology company Cellectis considered the possibility of expanded funding for a program that will test / confirm the clinical effectiveness of the UCART 19 development in large groups of patients. The first stage of the survey is scheduled for early 2016.
“A series of clinical trials of the first genetic edition of UCART is already on the horizon. Their successful completion could mark the beginning of a revolution in cancer immunotherapy.” Said Dr. Andre Chowlik, part-time CEO of Cellectis.
Note that genetically modified human cells have been used to treat cancer earlier, and work in this direction has been ongoing since a quarter century. So several adult patients were cured of leukemia in 2013. A vivid example is the case of 8-year-old Emily Whitehead from Philipsburg, suffering from lymphoblastic leukemia and becoming the first child at the University of Pennsylvania clinic who took part in the 2011 new gene drug testing program. The treatment was successful, after 2 years no signs of cancer were found in the girl. “It's amazing, you can take cells from a patient and make them into cells that attack a tumor,” said Dr. Janice Abkovitz, head of the Department of Blood Diseases at Washington University.
Emily Whitehead
In the described studies, the patient’s own cells were used as the “starting material”, in which a special gene was inserted, the purpose of which is to fight cancer cells. In the case of Leila, the number of healthy immune cells that could cope with the above task was not enough. Therefore, it was decided to use modified T cells of a healthy donor.
Today, clinical trials of gene therapy are being conducted in the case of some forms of congenital blindness, muscular dystrophy, hemophilia, and some promising approaches to blocking and treating HIV are being considered. And, according to experts, the victory over these serious ailments will be achieved first of all precisely by genetic modeling methods. In the future, the possibility of creating a set of populations of specific immune cells that are programmed to combat a particular type of infectious agent or cancer is being considered. This will mean that after making an accurate diagnosis to cure the patient it will be enough to introduce the corresponding modified cells into the blood. Having multiplied in the body, they will not only cope with the disease, but will also create effective protection against repeated illness of the same disease in the future.
Well, we wish a speedy amendment to Leila Richards and recovery to hundreds of thousands of cancer patients, for whom hope always dies last. And let the latest technologies help them in the very near future.
GOSH Hospital Learn
more about Leila Richards history and method on the Great Ormond Street Hospital official website . We invite our experts to share their views on the prospects of technology proposed by a joint group of researchers.
*****
Dear readers, we are always happy to meet and wait for you on the pages of our blog. We are ready to continue to share with you the latest news, review articles and other publications and will try to do our best to make the time spent with us useful for you. And, of course, do not forget to subscribe to our columns .
Our other articles and events