Latest paper from the father of CAR-T:
`CAR-T really completely cured cancer
`
`Latest paper from the father of CAR-T: CAR-T really completely cured cancer, the effect of
`more than ten years.
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`More than a decade later, when doctors announced that his cancer was cured, Doug Olson
`recalled the fall of 2010 when he participated in a clinical trial of CAR-T cell therapy, and he
`still remembers that he was full of excitement and hope for the scientific experiment.
`
`He said that when he was doing scientific research, like many young scientists, he dreamed
`of making a discovery that would have an impact on human beings, but he never thought
`that it would end up in this way—as a patient participating in a CAR that changes the way of
`cancer treatment- T clinical trials.
`
`The rise of cancer immunotherapy has brought new hope to the majority of cancer patients.
`
`Among them, CAR-T cell therapy has proven to be a powerful weapon against blood
`cancers.
`
`However, little is known about the long-term potential and clonal stability of these
`genetically engineered CAR-T cells reinfused into cancer patients.
`
`Doug Olson , an unfortunate patient with chronic lymphocytic leukemia (CLL) , was
`diagnosed in 1996 with CLL, a slow-growing but incurable leukemia.
`
`After years of chemotherapy, his condition continued to progress, at which point he began
`to consider a bone marrow transplant. David Porter , his attending doctor at the time, told
`him that the University of Pennsylvania was about to start a clinical trial of CAR-T cell
`therapy.
`
`After reading the trial protocol, he felt promising in the medical industry and decided to
`participate in the clinical trial.
`
`On September 13, 2010, he became the second leukemia patient in the world to receive
`CAR-T cell therapy.
`
`UPenn Ex. 2036
`Miltenyi v. UPenn
`IPR2022-00855
`Page 1
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`The doctors who formulated the treatment plan for him included Carl June and David Porter,
`but no one knew what CAR-T cell therapy was at the time.
`
`What kind of effect can be achieved, they hoped that these genetically engineered CAR-T
`cells could survive in the body for a month, and even dared not expect to cure leukemia.
`
`After a few weeks of CAR-T cell therapy, Doug Olson had no cancer cells in his body. After
`doctors told him the news, he was very optimistic that he had gotten rid of the cancer, but
`his doctors were not so sure.
`
`The time has come to 2022, more than a decade has passed, Doug OlsonThe CAR-T cells
`in the body are still working normally, and he is still in remission. During this period, Carl
`June was also known as the father of CAR-T for his contributions to CAR-T .
`
`Now, he says, it’s now conceivable that CAR- T curesDoug Olson, CAR-T can really cure
`leukemia.
`
`On February 2, 2022, Carl June et al. published a paper titled: Decade-long leukaemia
`remissions with persistence of CD4+ CAR T cells in Nature , detailing Bill Ludwig and the
`first patient in the world to receive CAR-T therapy .
`
`The treatment results of two CAR-T-treated Doug Olsons , who have not detected any signs
`of leukemia for more than ten years after treatment , but unfortunately, Bill Ludwig died of
`COVID-19 pneumonia in January 2021.
`
`This study provides a proof-of-concept for the long-term therapeutic efficacy and safety of
`integration into the body of CAR-T cell therapy .
`
`CAR-T cells are the natural anti-infection and anti-cancer immune cells T cells from the
`blood of cancer patients are genetically reprogrammed in vitro to express receptor proteins
`that can recognize specific antigens on cancer cells in the patient, which is the so-called
`chimeric antigen receptor (CAR ) .
`
`These genetically engineered CAR-T cells are then expanded using cell culture techniques
`and reinjected into patients to attack cancer cells.
`
`Since 2017, the US FDA has successively approved five CAR-T cell therapies for the
`treatment of leukemia, lymphoma and myeloma.
`
`UPenn Ex. 2036
`Miltenyi v. UPenn
`IPR2022-00855
`Page 2
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`Carl June estimates that tens of thousands of people around the world have now received
`CAR-T cell therapy.
`
`
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`
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`Although CAR-T has brought great hope to cancer patients, especially blood cancer
`patients, the therapy also has many limitations – very expensive, high risk of treatment, and
`high technical difficulty .
`
`Therefore, at present, CAR-T is still used as the last resort after other conventional
`treatment methods are ineffective.
`
`
`
`In addition, although some patients have achieved long-term remission after receiving CAR-
`T therapy, not every patient is so lucky, in the beginning, only about 25%-35% of chronic
`lymphocytic leukemia (CLL) are receiving CAR-T therapy after complete remission.
`
`Since then, with the improvement of technology, this proportion has increased year by year,
`but some patients who were in complete remission have still relapsed.
`
`Therefore, long-term follow-up studies of cancer patients receiving CAR-T therapy can
`reveal which factors contribute to durable remission, which is particularly important for
`improving CAR-T therapy and improving cancer cure rates.
`
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`
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`For more than a decade, Carl June et al. analyzed and studied the incidence of CD19 -
`targeted CAR-T therapy in 2010.Doug Olsonand Bill Ludwig , tracking their CAR-T cells and
`looking for any possible safety issues.
`
`
`
`
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`More than a decade later, they can still detect the presence of the CAR-T cells infused that
`year, and the two patients still have no signs of leukemia.
`
`It is unclear whether the CAR-T cells killed all the leukemia cells shortly after infusion, or
`whether the CAR-T cells, while circulating in the body, were able to eliminate the leukemia
`cells before they reached detectable levels.
`
`Notably, both patients developed highly activated CD4+ T cell populations that dominated
`the late CAR-T cell population (over 95%) .
`
`This transition is reflected in the stabilization of the CAR-T cell clonal composition,
`dominated by a small number of clones. Single-cell analysis showed that these long-lived
`CD4+ CAR-T cells exhibited cytotoxicity characteristics and sustained functional activation
`and proliferation.
`
`In addition, the initial response phase of one of the patients showed a γδ CAR-T cell
`population accompanied by a significant expansion of CD8+ CAR-T cells.
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`UPenn Ex. 2036
`Miltenyi v. UPenn
`IPR2022-00855
`Page 3
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`The identification and characterization of these unexpected CAR-T cell populations provides
`new insights into CAR-T cell signatures associated with anticancer response and long-term
`remission, the research team said.
`
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`Doug Olson , a healthcare worker, returned to medical diagnostics after a few years of
`CAR-T therapy, while he started exercising and running a half-marathon.
`
`He joked that he was cured of cancer, but did not want to end up dying of a heart attack. In
`order to help more cancer patients, he chose to publish his story of cancer treatment and
`recovery, so that more cancer patients can see hope.
`
`He said: “It may not be possible to cure their cancer today, but it is possible that something
`good is about to happen.
`
`Reference :
`https://www.nature.com/articles/s41586-021-04390-6
`
`Latest paper from the father of CAR-T: CAR-T really completely cured cancer
`
`(source:internet, reference only)
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`UPenn Ex. 2036
`Miltenyi v. UPenn
`IPR2022-00855
`Page 4
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