IGKV3 proteins as candidate "off-the-shelf" vaccines for kappa-light chain-restricted B-cell non-Hodgkin lymphomas

Martorelli, Debora, Guidoboni, Massimo, De Re, Valli, Muraro, Elena, Turrini, Riccardo, Merlo, Anna, Pasini, Elisa, Caggiari, Laura, Romagnoli, Luca, Spina, Michele, Mortarini, Roberta, Gasparotto, Daniela, Mazzucato, Mario, Carbone, Antonino, Rosato, Antonio, Anichini, Andrea and Dolcetti, Riccardo (2012) IGKV3 proteins as candidate "off-the-shelf" vaccines for kappa-light chain-restricted B-cell non-Hodgkin lymphomas. Clinical Cancer Research, 18 15: 4080-4091. doi:10.1158/1078-0432.CCR-12-0763


Author Martorelli, Debora
Guidoboni, Massimo
De Re, Valli
Muraro, Elena
Turrini, Riccardo
Merlo, Anna
Pasini, Elisa
Caggiari, Laura
Romagnoli, Luca
Spina, Michele
Mortarini, Roberta
Gasparotto, Daniela
Mazzucato, Mario
Carbone, Antonino
Rosato, Antonio
Anichini, Andrea
Dolcetti, Riccardo
Title IGKV3 proteins as candidate "off-the-shelf" vaccines for kappa-light chain-restricted B-cell non-Hodgkin lymphomas
Journal name Clinical Cancer Research   Check publisher's open access policy
ISSN 1078-0432
1557-3265
Publication date 2012-08-01
Sub-type Article (original research)
DOI 10.1158/1078-0432.CCR-12-0763
Open Access Status Not Open Access
Volume 18
Issue 15
Start page 4080
End page 4091
Total pages 12
Place of publication Philadelphia, PA United States
Publisher American Association for Cancer Research
Language eng
Formatted abstract
Purpose: An increasing set of B-cell non-Hodgkin lymphomas (B-NHL) show a biased usage of IGKV3-20 and IGKV3-15 immunoglobulin genes, a feature that could be exploited for the development of ready-to-use, broadly applicable cancer vaccines.

Experimental Design: The immunogenic properties of clonal IGKV3-20 and IGKV3-15 proteins were analyzed with particular focus on their ability to elicit cross-reactive responses against molecularly related IGKV proteins expressed by different B-cell lymphoproliferative disorders.

Results: IGK+ lymphoma patients show humoral and T-cell responses to IGKV3-20 and IGKV3-15 proteins and IGKV3-specific cytotoxic T lymphocytes (CTL) can be easily induced ex vivo. IGKV3-20–specific CTLs cross-react against different IGKV3 proteins, an effect mediated by the presence of 21 shared, sometimes promiscuous, T-cell epitopes, presented by common HLA class I allele products, thus assuring a broad HLA coverage of IGKV3-based vaccines. Many natural epitope variants are carried by IGK light chains expressed by a broad spectrum of B-NHLs and we show that IGKV3-20–specific CTLs cross-react also against several of these variant epitopes. Both humoral and CTL-specific responses were induced by KLH-conjugated IGKV3-20 protein in HLA-A2-transgenic mice and coinjection of IGKV3-20–specific CTLs with IGKV3-20+ or IGKV3-15+ lymphoma cells into SCID mice totally prevented tumor growth, thus confirming the ability of these effectors to mediate efficient and cross-reactive cytotoxic responses also in vivo.

Conclusions: These results provide the rationale to exploit IGKV3 proteins as “off-the-shelf” vaccines for a large fraction of lymphoma patients.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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