T-cell-epitope mapping of the idiotypic monoclonal IgG heavy and light chains in multiple myeloma

Fagerberg, Jan; Yi, Qing; Gigliotti, Dulceaydee; Harmenberg, Ulrika; Rudén, Ulla; Persson, Bengt L.; Österborg, Anders; Mellstedt, Håkan

doi:10.1002/(sici)1097-0215(19990301)80:5<671::aid-ijc7>3.0.co;2-e

Cited by 45 publications

(38 citation statements)

References 36 publications

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“…Our results also demonstrate that the immune response may be directly against the idiotypic determinants because the T cells responded only to the autologous Id protein, not to the allogeneic or isotype-matched Id proteins. Furthermore, we and others 11,28,29 have shown that T-cell responses induced by Id proteins also were against synthetic peptides corresponding to the complementarity-determining region I-III of the Id proteins. CTL recognition of target cells through their T-cell receptors activates 2 distinct mechanisms of cell lysis.…”

Section: Discussionmentioning

confidence: 66%

“…The observation is in agreement with some previous studies showing that the Id produced by malignant B cells contains tumor-specific protein sequences that stimulated CD4 ϩ and CD8 ϩ T cells. [23][24][25][26][27][28][29] Furthermore, the cytokine release by the CTLs was analyzed by the ELISPOT assay. The production of a significant amount of IFN-␥ and TNF-␣ was observed when the CTLs were restimulated with Id-pulsed DCs.…”

Section: Discussionmentioning

confidence: 99%

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Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells

Wen

Barlogie

2001

Blood

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116

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells

Wen

Barlogie

2001

Blood

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116

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“…The existence of naturally occurring leukaemic cell and tumour IgVH-CDR3-specific T-cells in B-CLL 4,15,19,20 as well as in multiple myeloma and B-cell lymphoma [21][22][23] has been reported earlier. Thus, tumour cells exhibit antigenic epitopes capable of inducing a tumour-specific cellular response.…”

Section: Dc-based Vaccines In B-cll P Kokhaei Et Almentioning

confidence: 66%

Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell–tumour hybrids in B-CLL

et al. 2003

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Dendritic cells (DC) are professional (specialised) antigenpresenting cells that can capture antigen from apoptotic tumour cells and induce MHC class I-and II-restricted responses. Also, DC fused with tumour cells may be effective for immune response induction. Both cell preparations may be considered as vaccine candidates in a therapeutic approach. We examined autologous T-cell activation by DC that had endocytosed leukaemic B-cell apoptotic bodies (Apo-DC) and compared it to the T-cell stimulatory capacity of DC that were fused with tumour cells. Following incubation, 22.676.2 (mean7s.e.m.) of DC had endocytosed leukaemic cells, while the frequency of DC-leukaemic cell hybrids was 10.572.6%. Apo-DC and hybrid cells both demonstrated the ability to stimulate a tumour-specific T-cell immune response in vitro. A T-cell proliferation response was also observed in four out of five CLL patients when using Apo-DC. However, fusion hybrids lacked the ability to elicit a proliferative response. Apo-DC also induced an IFN-c response, as did hybrid cells. The cytokine response induced by Apo-DC was significantly higher than that induced by fusion (Po0.05). This study shows that endocytosed apoptotic tumour cells induced a significantly stronger T-cell response than DC hybrids; and as such should be a better candidate for vaccine production.

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“…Although peptides derived from L chain CDRs may express T cell epitopes, anti-Id T cell reactivity is mostly directed against peptides derived from H chain CDRs, especially from the V-D-J (V H -D-J H ) CDR3 region. The predominance of immunity against H chains has been observed in many Id-vaccination studies in multiple myeloma and lymphoma patients (47)(48)(49)(50)(51). This general predominance of Id-specific T cell responses directed against sequences of H chain CDRs, especially CDR3, is attributed to the much larger versatility of H chains, which is mainly determined by their D segment (49).…”

Section: Discussionmentioning

confidence: 96%

Dendritic Cell-Based Therapeutic Vaccination against Myeloma: Vaccine Formulation Determines Efficacy against Light Chain Myeloma

Cohen

Haimovich

Hollander

2009

The Journal of Immunology

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Multiple myeloma is an incurable plasma cell malignancy. Immunotherapy in myeloma patients had limited success to date. We have previously demonstrated that dendritic cells (DCs) pulsed with autologous Ig Id induced Id-reactive CD8+ T cells and protection against a myeloma tumor challenge. In this work, we studied the therapeutic efficacy of chemotherapy combined with different formulations of DC-based vaccines in mice bearing large plasma cell tumors. The comparative study demonstrated that s.c. injection of DCs loaded with Id coupled to keyhole limpet hemocyanin, s.c. injection of DCs loaded with irradiated tumor cells, and intratumoral injection of naive DCs were similarly effective in mediating tumor regression and long-term survival. However, whereas the Id-keyhole limpet hemocyanin-DC vaccine was inefficient against myeloma cells that lost expression of the Ig H chain, intratumoral injection of naive DCs and s.c. injection of DCs loaded with irradiated tumor cells were highly effective against cells producing L chains only. This may be of particular importance for patients with L chain myeloma. Given that T cells respond primarily to peptides derived from H chain CDRs, attempts to treat L chain disease with myeloma protein-pulsed DCs may be futile. Vaccination with tumor cell-loaded DCs may, however, induce an effective antitumor response.

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T-cell-epitope mapping of the idiotypic monoclonal IgG heavy and light chains in multiple myeloma

Cited by 45 publications

References 36 publications

Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells

Idiotype-specific cytotoxic T lymphocytes in multiple myeloma: evidence for their capacity to lyse autologous primary tumor cells

Dendritic cells loaded with apoptotic tumour cells induce a stronger T-cell response than dendritic cell–tumour hybrids in B-CLL

Dendritic Cell-Based Therapeutic Vaccination against Myeloma: Vaccine Formulation Determines Efficacy against Light Chain Myeloma

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