Immunotherapy in liver tumors: II. Intratumoral injection with activated tumor-infiltrating lymphocytes, intrasplenic administration of recombinant interleukin-2 and interferon α causes tumor regression and lysis

Liu, David L.; Håkansson, C. H.; Seifert, J.

doi:10.1016/0304-3835(94)90236-4

Cited by 12 publications

(3 citation statements)

References 10 publications

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“…Indeed, several conventional chemotherapeutic agents have immunostimulatory effects through the induction of the immunogenic cell death (ICD), which stimulates both the innate and adaptive immune systems. 9,[81][82][83][84][85][86][87] Moreover, the proliferative and/or functional capacities of adoptively transferred cells can be boosted by multiple cytokines including IL-2, IL-7 or IL-15, 16,[88][89][90][91] while their activation status and tumor homing ability can be improved with TLR agonists [92][93][94][95][96] or angiogenesis inhibitors, [97][98][99] respectively. Finally, to be fully effective, infused lymphocytes need to evolve in a permissive microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Trial Watch: Adoptively transferred cells for anticancer immunotherapy

et al. 2017

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Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated , and administered to lymphodepleted patients. ACT may be optionally associated with chemo- and/or immunotherapeutics, with the overall aim of enhancing the proliferation, persistence and functionality of infused cells, as well as to ensure their evolution in an immunological permissive local and systemic microenvironment. In addition, isolated lymphocytes can be genetically engineered to endow them with the ability to target a specific tumor-associated antigen (TAA), to increase their lifespan, and/or to reduce their potential toxicity. The infusion of chimeric antigen receptor (CAR)-expressing cytotoxic T lymphocytes redirected against CD19 has shown promising clinical efficacy in patients with B-cell malignancies. Accordingly, the US Food and Drug Administration (FDA) has recently granted 'breakthrough therapy' designation to a CAR-based T-cell therapy (CTL019) for patients with B-cell malignancies. Considerable efforts are now being devoted to the development of efficient ACT-based immunotherapies for non-hematological neoplasms. In this Trial Watch, we summarize recent clinical advances on the use of ACT for oncological indications.

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Section: Introductionmentioning

confidence: 99%

Trial Watch: Adoptively transferred cells for anticancer immunotherapy

et al. 2017

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“…It has been tested in clinical trials as an anticancer agent, has been demonstrated to be effective in numerous immunotherapy applications,2–4 and has been approved by the FDA for the treatment of metastatic renal cell carcinoma as well as metastatic melanoma. There is definitive evidence of its efficacy in combination with exogenous immune cells and other cytokines in the treatment of solid tumor malignancies 5–9…”

Section: Introductionmentioning

confidence: 99%

Efficient strategies for the conjugation of oligonucleotides to antibodies enabling highly sensitive protein detection

et al. 2004

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Three methods for the conjugation of oligonucleotides to antibodies and the subsequent application of these conjugates to protein detection at attomole levels in immunoassays are described. The methods are based on chemical modification of both antibody and oligonucleotide. Aldehydes were introduced onto antibodies by modification of primary amines or oxidation of carbohydrate residues. Aldehyde- or hydrazine-modified oligonucleotides were prepared either during phosphoramidite synthesis or by post-synthesis derivatization. Conjugation between the modified oligonucleotide and antibody resulted in the formation of a hydrazone bond that proved to be stable over long periods of time under physiological conditions. The binding activity of each antibody-oligonucleotide conjugate was determined to be comparable to the corresponding unmodified antibody using a standard sandwich ELISA. Each oligonucleotide contained a unique DNA sequence flanked by universal primers at both ends and was assigned to a specific antibody. Highly sensitive immunoassays were performed by immobilizing analyte for each conjugate onto a solid support with cognate capture antibodies. Binding of the antibody-oligonucleotide conjugate to the immobilized analyte allowed for amplification of the attached DNA. Products of amplification were visualized using gel electrophoresis, thus denoting the presence of bound analyte. The preferred conjugation method was used to generate a set of antibody-oligonucleotide conjugates suitable for high-sensitivity protein detection.

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“…Intratumoral T-cell therapy could be an option to solve this problem. In a mouse liver tumor model, intratumoral injection with activated TILs and simultaneous administration of recombinant interleukin 2 (rIL-2) and IFNα was more effective in regressing the mouse liver tumor than the IL-2 + IFNα combination [119]. A case reported that intratumoral adoptive immunotherapy with TILs in patients with melanoma, in combination with subcutaneous infusion of IL-2 and a single intratumoral injection of a low dose of IFNα, led to consistent tumor regression [63].…”

Section: Cellsmentioning

confidence: 99%

Immunotherapeutic Agents for Intratumoral Immunotherapy

Shyr,

Liu,

Chien

et al. 2023

Vaccines

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Immunotherapy using systemic immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cells has revolutionized cancer treatment, but it only benefits a subset of patients. Systemic immunotherapies cause severe autoimmune toxicities and cytokine storms. Immune-related adverse events (irAEs) plus the immunosuppressive tumor microenvironment (TME) have been linked to the inefficacy of systemic immunotherapy. Intratumoral immunotherapy that increases immunotherapeutic agent bioavailability inside tumors could enhance the efficacy of immunotherapies and reduce systemic toxicities. In preclinical and clinical studies, intratumoral administration of immunostimulatory agents from small molecules to xenogeneic cells has demonstrated antitumor effects not only on the injected tumors but also against noninjected lesions. Herein, we review and discuss the results of these approaches in preclinical models and clinical trials to build the landscape of intratumoral immunotherapeutic agents and we describe how they stimulate the body’s immune system to trigger antitumor immunity as well as the challenges in clinical practice. Systemic and intratumoral combination immunotherapy would make the best use of the body’s immune system to treat cancers. Combining precision medicine and immunotherapy in cancer treatment would treat both the mutated targets in tumors and the weakened body’s immune system simultaneously, exerting maximum effects of the medical intervention.

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Immunotherapy in liver tumors: II. Intratumoral injection with activated tumor-infiltrating lymphocytes, intrasplenic administration of recombinant interleukin-2 and interferon α causes tumor regression and lysis

Cited by 12 publications

References 10 publications

Trial Watch: Adoptively transferred cells for anticancer immunotherapy

Trial Watch: Adoptively transferred cells for anticancer immunotherapy

Efficient strategies for the conjugation of oligonucleotides to antibodies enabling highly sensitive protein detection

Immunotherapeutic Agents for Intratumoral Immunotherapy

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