Paul Aebersold's research while affiliated with National Cancer Institute (USA) and other places
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Publications (15)
Treatment using interleukin-2 (IL-2) alone or in conjunction with lymphokine-activated killer (LAK) cells has been shown to mediate disease regression in selected patients with advanced cancer.
This prospective randomized trial was designed to determine whether the administration of LAK cells in conjunction with high-dose IL-2 alters response and s...
Tumor-infiltrating lymphocytes (TILs) can be grown in vitro in medium containing interleukin-2 (IL-2). In clinical trials at the Surgery Branch of the National Cancer Institute, patients with metastatic malignant melanomas were treated with IL-2 plus the adoptive transfer of autologous TILs. At the time of treatment, TILs were assayed for in vitro...
The application of bone marrow gene therapy has been stalled by the inability to achieve stable high-level gene transfer and expression in the totipotent stem cells. We show that retroviral vectors can stably introduce genes into antigen-specific murine and human T lymphocytes in culture. Murine helper T cells were transduced with the retroviral ve...
Congenitally immune-deficient bg/nu/xid (BNX) mice are severely compromised in their ability to mount T-cell, B-cell, and lymphokine-activated killer (LAK) cell responses. Successful engraftment of BNX mice with human hematopoietic stem cells has been demonstrated recently. We have investigated the potential use of BNX mice for studies relating to...
Studies were undertaken to test the susceptibility of individual T cell subpopulations to retroviral-mediated gene transduction. Gene transfer into human tumor-infiltrating lymphocytes (TIL) or peripheral blood mononuclear cells (PBMC) was carried out by transduction with an amphotropic murine retroviral vector (LNL6 or N2) containing the bacterial...
Treatment with tumor-infiltrating lymphocytes (TIL) plus interleukin-2 can mediate the regression of metastatic melanoma in approximately half of patients. To optimize this treatment approach and define the in vivo distribution and survival of TIL, we used retroviral-mediated gene transduction to introduce the gene coding for resistance to neomycin...
Human tumor infiltrating lymphocytes (TIL) from metastatic melanoma of six patients were grown using a new hollow fiber bioreactor system. After inoculating 0.35-10 X 10(8) TIL into the extra-fiber space (EFS), each Cellmax bioreactor was perfused with AIM-V medium, supplemented with rIL-2. The cells subsequently expanded 124-1170-fold to yield 1.5...
Patients with malignant melanoma have been treated with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes (TIL) marked by retroviral gene transduction. The retroviral vector contained a gene coding for the bacterial enzyme neomycin phosphotransferase, such that transduced TIL expressing the enzyme could survive otherwise toxic concentrations...
Tumor-infiltrating lymphocytes (TILs) are cells generated from tumor suspensions cultured in interleukin 2 that can mediate cancer regression when adoptively transferred into mice or humans. Since TILs proliferate rapidly in vitro, recirculate, and preferentially localize at the tumor site in vivo, they provide an attractive model for delivery of e...
31P NMR spectra of tumor-infiltrating lymphocytes (TILs) were found to be significantly different from those of normal peripheral lymphocytes. The greatest difference was in the phosphodiester (PDE) region, mainly in the glycerophosphocholine (GPC) signal. Short-term activation of peripheral lymphocytes with interleukin-2 induced a small increase i...
Patients with metastatic melanoma undergoing therapy with cyclophosphamide (CPM), tumor-infiltrating lymphocytes (TIL), and interleukin-2 (IL-2) were studied for the ability of their 111In-labeled TIL or peripheral blood lymphocytes (PBL) to localize in sites of tumor using gamma camera imaging and biopsies. Nineteen infusions of radiolabeled TIL w...
We have administered 1039 courses of high-dose interleukin-2 (IL-2) to 652 cancer patients. Five hundred ninety-six patients had metastatic cancer that either had failed standard effective therapies or had disease for which no standard effective therapy existed, and 56 patients were treated in the absence of evaluable disease in the adjuvant settin...
Lymphocytes extracted from freshly resected melanomas can be expanded in vitro and can often mediate specific lysis of autologous tumor cells but not allogeneic tumor or autologous normal cells. We treated 20 patients with metastatic melanoma by means of adoptive transfer of these tumor-infiltrating lymphocytes and interleukin-2, after the patients...
The administration of lymphokine-activated killer (LAK) cells along with interleukin-2 (IL-2) can mediate regression of tumors in selected patients. A closed automated system utilizing commercial blood cell separators has been developed for washing and Ficoll-Hypaque (FH) separation of lymphocytes, for lymphocyte culture in polyolefin bags, and for...
Citations
... China embraced gene therapy at a very early time. The first clinical trial of gene therapy in China dates back to 1991-just 1 year after the first-ever gene therapy performed at the National Institutes of Health (NIH) in 1990 [11,12]. In addition, China approved the world's first gene therapy product in 2003-Gendicine-which is an oncolytic adenovirus equipped with p53 for the treatment of advanced head and neck cancer. ...
... Based on these results, the same group studied the safety of reinfusion of genetically modified NeoR-TILs in five MM patients. No adverse effects were reported, PCR analysis detected NeoR-TILs in the circulation after three weeks and in the tumor deposits after 64 days (66,80), and long-term viable NeoR-TILs after cell infusion were observed (67). ...
... For all other studies, animals were injected with one SKOV3ip.1-vector (clone 3) or HA-MKK4 cell line (clone 2) and sacrificed at the experimental end points (3,14,30, or 60 dpi). ...
... In contrast, cancer gene therapy holds promise as a new treatment strategy [5][6][7][8][9] . In 1991, the first clinical trial of cancer gene therapy demonstrated that genetically modified immune cells can be successfully reintroduced into patients 10,11 , and subsequent approval of chimeric antigen receptor T cell therapy by the US Food and Drug Administration resulted in remarkable advances in this field. ...
... The approach was aimed not to treat the disease, but to demonstrate the feasibility of the retroviral vectors to stably modify the cells. The marker gene, encoding bacterial neomycin transferase, was incorporated into the retroviral backbone and the tumor-infiltrating lymphocytes of the patient collected two months after delivery demonstrated its expression (Rosenberg et al., 1990;Culver et al., 1991). ...
Reference: Gene therapy. The legacy of Wacław Szybalski
... investigated matching tumor growth curves using time variant carrying capacity (Hahnfeldt et al., 1999), or modeling the effect of radiation therapy as a decrease in the carrying capacity (Zahid et al., 2021). Lastly, individuals with metastatic melanoma with a shorter tumor infiltrating lymphocyte doubling time had a higher response frequency to treatment with autologous tumor-infiltrating lymphocytes and interleukin 2 (Aebersold et al., 1991;Rosenberg et al., 1994). The PD-L1 expression level per tumor cell was taken from in vitro data of INF-γ treated tumor cells. ...
... Hollow fiber bioreactor, as a valuable method for generating large quantities of primary human lymphocytes for experimental and clinical uses, was described 30 years ago by Knazek et al. [89]. These bioreactors are made of a large number of collateral, semipermeable, hollow fibers located in a tubular housing [90]. ...
... Over the past decades, NA drugs including DNA-and RNA-based therapeutics, have been widely exploited to treat a wide range of diseases, especially genetic disorders, and cancers. The first attempt to deliver a gene coding for resistance to neomycin into lymphocytes harvested from cancer patients was published 30 years ago 15 . After decades of promises, tempered by great deal of failures, NA-based therapies targeting the gene(s) responsible(s) for various human diseases have now become promising therapeutic tools. ...
... In particular, adoptive cell therapy (ACT) is based on the expansion of antigen-specific lymphocytes, autologous or genetically engineered to ensure the recognition of tumours after re-infusion at the location of the cancer (Klapper et al., 2009;Somerville et al., 2012). It is one of the first examples of gene transfer to human approved for therapy after pioneering works in the early 1990s (Bonini and Mondino, 2015;Kasid et al., 1990;Rosenberg et al., 1990). However, millions of such T cells are required for a single therapy, and this number cannot be obtained through direct harvesting from donors only (Somerville et al., 2012). ...
... Human lymphocytes represent terminally differentiated cells. De-differentiated lymphoblasts were obtained through lymphocyte activation by interleukin 2, which is known to induce prolyferation of lymphocytes [23][24][25][26]. The lymphoblasts were cultivated for 24 or 44 h before the preparation of nucleoids. ...
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