• Biomolecules & Therapeutics
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• 제32권4호
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• pp.424-431
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• 2024

Among the therapeutic strategies in cancer immunotherapy-such as immune-modulating antibodies, cancer vaccines, or adoptive T cell transfer-T cells have been an attractive target due to their cytotoxicity toward tumor cells and the tumor antigen-specific binding of their receptors. Leveraging the unique properties of T cells, chimeric antigen receptor-T cells and T cell receptor (TCR)-T cells were developed through genetic modification of their receptors, enhancing the specificity and effectiveness of T cell therapy. Adoptive cell transfer of chimeric antigen receptor-T cells has been successful for the treatment of hematological malignancies. To expand T cell therapy to solid tumors, T cells are modified to express defined TCR targeting tumor associated antigen, which is called TCR-T therapy. This review discusses anti-tumor T cell therapies, with a focus on engineered TCR-T cell therapy. We outline the characteristics of TCR-T cell therapy and its clinical application to non-hematological malignancies.

• Biomolecules & Therapeutics
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• 제30권4호
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• pp.299-308
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• 2022

T cells are attractive targets for the development of immunotherapy to treat cancer due to their biological features, capacity of cytotoxicity, and antigen-specific binding of receptors. Novel strategies that can modulate T cell functions or receptor reactivity provide effective therapies, including checkpoint inhibitor, bispecific antibody, and adoptive transfer of T cells transduced with tumor antigen-specific receptors. T cell-based therapies have presented successful pre-clinical/clinical outcomes despite their common immune-related adverse effects. Ongoing studies will allow us to advance current T cell therapies and develop innovative personalized T cell therapies. This review summarizes immunotherapeutic approaches with a focus on T cells. Anti-cancer T cell therapies are also discussed regarding their biological perspectives, efficacy, toxicity, challenges, and opportunities.

• BMB Reports
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• 제55권1호
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• pp.39-47
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• 2022

Adoptive cell transfer (ACT), a form of cell-based immunotherapy that eliminates cancer by restoring and strengthening the body's immune system, has revolutionized cancer treatment. ACT entails intravenous transfer of either tumor-resident or peripheral blood-modified immune cells into cancer patients to mediate anti-tumor response. Although these immune cells control and eradicate cancer via enhanced cytotoxicity against specific tumor antigens, several side effects have been frequently reported in clinical trials. Recently, exosomes, potential cell-free therapeutics, have emerged as an alternative to cell-based immunotherapies, due to their higher stability under same storage condition, lower risk of GvHD and CRS, and higher resistance to immunosuppressive tumor microenvironment. Exosomes, which are nano-sized lipid vesicles, are secreted by living cells, including immune cells. Exosomes contain proteins, lipids, and nucleic acids, and the functional role of each exosome is determined by the specific cargo derived from parental cells. Exosomes derived from cytotoxic effectors including T cells and NK cells exert anti-tumor effects via proteins such as granzyme B and FasL. In this mini-review, we describe the current understanding of the ACT and immune cell-derived exosomes and discuss the limitations of ACT and the opportunities for immune cell-derived exosomes as immune therapies.

• Journal of Periodontal and Implant Science
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• 제35권1호
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• pp.1-8
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• 2005

Bacterial heat shock protein has been one of the components that are responsible to induce autoimmune disease mechanisms in the pathogenesis of atherosclerosis due to high level of homology in sequence with human counterpart. This mechanism may explain how bacterial infectious disease, such as periodontal disease, might contribute to the acceleration of the disease process of atherosclerosis. Porphyromonas gingivalis which is a major periodontal pathogenic bacterial species, has been implicated as one of the pathogenic bacteria playing the role in this context. The present study has been performed to evaluate the anti-atherosclerotic effect of adoptive transfer of Porphyromonas gingivalis heat shock protein epitope-specific T cell lines into severe combined immunodeficiency (SCID) mice. Peptide no. 15 with amino acid sequence VKEVASKTND-specific T cell line was selected for the transfer. When experimental atherosclerosis was induced in SCID mice adoptively transferred either by the T cell lines (experimental group) or by non-specific mouse T cells (control group), there was no significant difference in the severity and extent of the atherosclerosis induced by hypercholesterol diet.

• IMMUNE NETWORK
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• 제16권5호
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• pp.281-285
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• 2016

CD4⁺ regulatory T cells (Tregs) are essential for normal immune surveillance, and their dysfunction can lead to the development of autoimmune diseases, such as type-1 diabetes (T1D). T1D is a T cell-mediated autoimmune disease characterized by islet b cell destruction, hypoinsulinemia, and severely altered glucose homeostasis. Tregs play a critical role in the development of T1D and participate in peripheral tolerance. Pluripotent stem cells (PSCs) can be utilized to obtain a renewable source of healthy Tregs to treat T1D as they have the ability to produce almost all cell types in the body, including Tregs. However, the right conditions for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) remain undefined, especially molecular mechanisms that direct differentiation of such Tregs. Auto Ag-specific PSC-Tregs can be programmed to be tissue-associated and infiltrate to local inflamed tissue (e.g., islets) to suppress autoimmune responses after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. Developing auto Ag-specific PSC-Tregs can reduce overall immunosuppression after adoptive transfer by accumulating inflamed islets, which drives forward the use of therapeutic PSC-Tregs for cell-based therapies in T1D.

• IMMUNE NETWORK
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• 제7권4호
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• pp.173-178
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• 2007

Background: We studied the role for expression of CD40 and CD40L by CD4 and CD8 T cells in the generation of CD8 T cell response to minor histocompatibility antigen, H60. H60 is a cellular antigen to which CD8 responses require CD4 T cell help. Methods: CD40- or CD40L-deficient mice were adoptively transferred with normal CD4 or CD8 T cells or with memory CD4 or CD8 T cells, and were immunized with male H60 congenic splenocytes to induce CD8 T cell response to H60. Peripheral blood CD8 T cell from the immunized mice were stained with the H60 tetramer. Results: CD8 T cell response to H60 was not induced in both CD40- and CD40L-deficient mice. Adoptive transfer of $CD40^{+/+}$ CD8 T cells into CD40-deficient mice did not compensate the defect in inducing CD8 T cell response to H60, while the H60-specific CD8 T cells were activated in the CD40-deficient mice that were adoptively transferred with $CD40^{+/+}$ CD4 T cells. Adoptive transfer of $CD40L^{+/+}$ CD4 T cells into CD40L-deficient mice induced primary CD8 T cell response for H60 and the presence of $CD40L^{+/+}$ CD4 T cells was required even for memory CD8 T cells response to H60. Conclusion: Our results suggest that the CD40-CD40L interaction mediates the delivery of CD4 T cell help to naive and memory H60-specific CD8 T cells. While the expression of CD40L by CD4 T cells is essential, signaling through CD40 on CD8 T cells is not required for the induction of CD8 T cell response to H60.

• IMMUNE NETWORK
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• 제4권1호
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• pp.31-37
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• 2004

Background: 1-8D gene is a member of human 1-8 interferon inducible gene family and is shown to be overexpressed in fresh colon cancer tissues. Three peptides 1-6, 3-5 and 3-7 derived from 1-8D gene were shown to have immunogenicity against colon cancer. Methods: To study tumor immunotherapy of these peptides we established an adoptive transfer model. $D^{b-/-}{\times}{\beta}2$ microglobulin (${\beta}2m$) null mice transgenic for a chimeric HLA-A2.1/$D^b-{\beta}2m$ single chain (HHD mice) were immunized with irradiated peptide-loaded RMA-S/HHD/B7.1 transfectants. Spleens were removed after last immunization, and splenocytes were re-stimulated in vitro. Lymphocytes from vaccinated HHD mice were transferred together with IL-2 to the tumor bearing nude mice that were challenged S.C. with the HCT/HHD/B7 colon carcinoma cell line that was found to grow in these mice. Results: Peptide 3-5 was found to be highly effective in CTL activity. Adoptively transferred anti-peptide 3-5 cytolytic T lymphocytes caused significant retardation in tumor growth. Conclusion: This study shows that peptide 3-5 can be the most effective candidate for the vaccine of adoptive immunotherapy against colon cancer.

• IMMUNE NETWORK
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• 제6권2호
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• pp.93-101
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• 2006

Background: Memory T lymphocytes of the immune system provide long-term protection in response to bacterial or viral infections/immunization. Ag concentration has also been postulated to be important in determining whether T cell differentiation favors effector versus memory cell development. In the present study we hypothesized that naive Ag-specific $CD4^+$ T cells briefly stimulated with different Ag doses at the primary exposure could affect establishment of memory cell pool after secondary immunization. Methods: To assess this hypothesis, the response kinetics of DO11.10 TCR $CD4^+$ T cells primed with different Ag doses in vitro was measured after adoptive transfer to naive BALB/c mice. Results: Maximum expansion was shown in cells primarily stimulated with high doses of ovalbumin peptide $(OVA_{323-339})$, whereas cells in vitro stimulated with low dose were expanded slightly after in vivo secondary exposure. However, the cells primed with low $OVA_{323-339}$ peptide dose showed least contraction and established higher number of memory cells than other treated groups. When the cell division was analyzed after adoptive transfer, the high dose Ag-stimulated donor cells have undergone seven rounds of cell division at 3 days post-adoptive transfer. However, there was very few division in naive and low dose of peptide-treated group. Conclusion: These results suggest that primary stimulation with a low dose of Ag leads to better memory $CD4^+$ T cell generation after secondary immunization. Therefore, these facts imply that optimally primed $CD4^+$ T cells is necessary to support effective memory pool following administration of booster dose in prime-boost vaccination.

• IMMUNE NETWORK
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• 제16권2호
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• pp.134-139
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• 2016

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

• BMB Reports
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• 제28권6호
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• pp.556-561
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• 1995

The purpose of this study was to establish an in vitro culture method of tumor-specific T cells, and determine the efficacy of the cultured tumor-specific cytotoxic T-lymphocytes (CTL) as an agent of anti-tumor immunotherapy against a murine lymphoma, TIMI.4. Tumor-specific T-lymphocytes derived from C57BL/6 mice (thy-1.2) immune to TIMI.4 were activated by in vitro stimulation with the irradiated TIMI.4 cells, and expanded by restimulation with TIMI.4 in the presence of the concanavalin A-stimulated rat spleen culture supernatant, and splenic antigen-presenting cells. In vitro restimulation enhanced markedly the proportion of $CD8^+$, a predominant surface marker of CTL and the cytotoxic activity in the cultured immune T cell population. The resulting TIMI.4-specific T cells were adoptively transferred into nude mice. The tumor cells residing in the host after 7 days of adoptive transfer to B6.PL (thy-1.1) mice were quantified by use of an antibody directed to the thy-1.2 allele. The TIMI.4 cells in the recipient nude mice were decreased in a dose-dependent manner. Anti-tumor activity of the TIMI.4-specific T cells was also demonstrated by a survival test, where the tumor-bearing nu/nu mice which received the activated T-cells survived about 30% longer than the control mice which received the tumor cells alone. These suggest that adoptive transfer of TIMI.4-specific T cells could be a candidate for effective therapy of the murine lymphoma.