scholarly journals Scaffolds that mimic antigen-presenting cells enable ex vivo expansion of primary T cells

2018 ◽  
Vol 36 (2) ◽  
pp. 160-169 ◽  
Author(s):  
Alexander S Cheung ◽  
David K Y Zhang ◽  
Sandeep T Koshy ◽  
David J Mooney
Keyword(s):  
T Cells ◽  
Ex Vivo ◽  
Antigen Presenting Cells ◽  
Ex Vivo Expansion ◽  
Antigen Presenting

scholarly journals Selective tumor antigen vaccine delivery to human CD169+antigen-presenting cells using ganglioside-liposomes

2020 ◽  
Vol 117 (44) ◽  
pp. 27528-27539
Author(s):  
Alsya J. Affandi ◽  
Joanna Grabowska ◽  
Katarzyna Olesek ◽  
Miguel Lopez Venegas ◽  
Arnaud Barbaria ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Antigen ◽  
Tumor Antigens ◽  
Ex Vivo ◽  
Antigen Presenting Cells ◽  
Dependent Manner ◽  
Cross Presentation ◽  
Vaccine Carrier ◽  
Antigen Presenting

Priming of CD8+T cells by dendritic cells (DCs) is crucial for the generation of effective antitumor immune responses. Here, we describe a liposomal vaccine carrier that delivers tumor antigens to human CD169/Siglec-1+antigen-presenting cells using gangliosides as targeting ligands. Ganglioside-liposomes specifically bound to CD169 and were internalized by in vitro-generated monocyte-derived DCs (moDCs) and macrophages and by ex vivo-isolated splenic macrophages in a CD169-dependent manner. In blood, high-dimensional reduction analysis revealed that ganglioside-liposomes specifically targeted CD14+CD169+monocytes and Axl+CD169+DCs. Liposomal codelivery of tumor antigen and Toll-like receptor ligand to CD169+moDCs and Axl+CD169+DCs led to cytokine production and robust cross-presentation and activation of tumor antigen-specific CD8+T cells. Finally, Axl+CD169+DCs were present in cancer patients and efficiently captured ganglioside-liposomes. Our findings demonstrate a nanovaccine platform targeting CD169+DCs to drive antitumor T cell responses.

Tregs Specific for Minor Histocompatibility Antigens

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1891-1891
Author(s):  
Anandharaman Veerapathran ◽  
Joseph Pidala ◽  
Francisca Beato ◽  
William E. Janssen ◽  
Xue-Zhong Yu ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Antigen Presenting Cells ◽  
Histocompatibility Antigens ◽  
Minor Histocompatibility Antigens ◽  
Sibling Pairs ◽  
Matched Sibling ◽  
Antigen Presenting

Abstract Abstract 1891 Background: The risk of acute GVHD after HSCT is increased in male recipients of female grafts. Disparities for the male-associated H-Y and other minor histocompatibility antigens (mHAs) have the capacity to sensitize alloreactive donor T cells and cause GVHD in HLA-matched recipients. These mHAs are polymorphic proteins that differ between donor and recipient and are presented as peptides by HLA molecules on recipient or donor antigen-presenting cells to donor immune cells. Currently, there is no evidence that minor histocompatibility antigen specific Tregs exist. Earlier in our laboratory, we have measured the frequency, growth requirements, and function of human blood Tregs specific for allo-MHC. In the present study, we sought to detect the frequency, expansion kinetics and characteristics of the minor antigens specific Tregs in the blood of HLA-matched sibling pair. Methods: CD4+CD25+CD127− Tregs were isolated by immunoabsorption from sibling donors, and cultured with HLA-matched sibling recipient antigen-presenting cells in the presence of IL-2, IL-15 and rapamycin. We detected 30–50 fold increase in H-TdR uptake at 6 days in Treg cultures stimulated by HLA-identical sibling compared to self DC. The precursor frequency of mHA-specific Tregs are between 7 and 43 (median - 13) cells per one million blood Tregs. The frequency of mHA-specific conventional CD4 T cells among total blood CD4 T cells is similar in HLA-matched sibling donors. Ex vivo expanded mHA-specific Tregs maintained higher levels of Foxp3 expression, retained the lymphoid homing receptor CD62L and a chemokine receptor, CCR7, suggesting that they are functional and are able to migrate to lymphoid tissue in vivo. Split well assay on day 12 demonstrated the mHA specificity, since Treg responded to restimulation with DC from the original HLA-identical sibling, but not self DC. The mHA-specific Tregs expanded to more than 100 fold in vitro, and exhibited antigen specific suppression. When Tregs were cultured at limiting dilution, we obtained 6 mHA-specific Treg clones that retained TGF-beta secretion in response to the sibling's mHA-disparate DC but not self DC. Conclusion: We demonstrated for the first time that it is possible to detect and expand mHA specific Tregs from HLA-matched sibling pairs, immunotherapy with mHA-specific Tregs may prevent GVHD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer

Blood ◽  
2007 ◽  
Vol 110 (8) ◽  
pp. 2838-2845 ◽  
Author(s):  
Catherine M. Bollard ◽  
Stephen Gottschalk ◽  
Ann M. Leen ◽  
Heidi Weiss ◽  
Karin C. Straathof ◽  
...  
Keyword(s):  
T Cells ◽  
Genetic Modification ◽  
Tumor Antigens ◽  
Ex Vivo ◽  
Antigen Presenting Cells ◽  
Bulky Disease ◽  
Barr Virus ◽  
Relapsed Disease ◽  
Antigen Presenting

AbstractEpstein-Barr virus (EBV)–associated tumors developing in immunocompetent individuals present a challenge to immunotherapy, since they lack expression of immunodominant viral antigens. However, the tumors consistently express viral proteins including LMP2, which are immunologically “weak” but may nonetheless be targets for immune T cells. We previously showed that a majority of cytotoxic T lymphocytes (CTLs) reactivated using EBV-transformed B-lymphoblastoid cells lines (LCLs) contained minor populations of LMP2-specific T cells and homed to tumor sites. However, they did not produce remissions in patients with bulky disease. We have now used gene transfer into antigen-presenting cells (APCs) to augment the expression and immunogenicity of LMP2. These modified APCs increased the frequency of LMP2-specific CTLs by up to 100-fold compared with unmodified LCL-APCs. The LMP2-specific population expanded and persisted in vivo without adverse effects. Nine of 10 patients treated in remission of high-risk disease remain in remission, and 5 of 6 patients with active relapsed disease had a tumor response, which was complete in 4 and sustained for more than 9 months. It is therefore possible to generate immune responses to weak tumor antigens by ex vivo genetic modification of APCs and the CTLs so produced can have substantial antitumor activity. This study is registered at http://www.cancer.gov/clinicaltrials (protocol IDs: BCM-H-9936, NCT00062868, NCT00070226).

Pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorates experimental autoimmune encephalomyelitis by suppressing the functions of antigen presenting cells

2004 ◽  
Vol 10 (6) ◽  
pp. 651-659 ◽  
Author(s):  
Hideki Kato ◽  
Atsushi Ito ◽  
Jun Kawanokuchi ◽  
Shijie Jin ◽  
Tetsuya Mizuno ◽  
...  
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Adenylate Cyclase ◽  
Ex Vivo ◽  
Antigen Presenting Cells ◽  
Significant Inhibition ◽  
Autoimmune Encephalomyelitis ◽  
Pituitary Adenylate Cyclase ◽  
Antigen Presenting ◽  
Experimental Autoimmune

Pituitary adenylate cyclase-activating polypeptide (PACAP), a 38-amino acid neuropeptide belonging to the secretin-glucagon-vasoactive intestinal peptide (VIP) family, performs a variety of functions in both the nervous and immune systems. In this study, we examined the effects of PACAP on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. When administrated intraperitoneally every other day after immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35 -55, PACAP ameliorated both the clinical and pathological manifestations of EAE. Ex vivo examination revealed a significant inhibition of MOG35 55-specific Th1 response in mice treated with PACAP.In vitro analysis revealed that PACAP suppressed the production of inflammatory cytokines, including TNF-a, IL-1b, and IL-12, and expression of the costimulatory factor B7-2 on macrophage and microglia, which may function as antigen presenting cells (APC) in the CNS. While PACAP suppressed the differentiation of MOG35 55-specific T cells into Th1 effectors upon restimulation with MOG35 55-expressing APC, it did not affect interferon (IFN)-g production by MOG35 55-specific T cells stimulated with anti-CD3 and anti-CD28. These observations suggested that PACAP suppressed induction of EAE primarily via suppression of APC function and inflammatory cytokine production. PACAP may be useful in the future treatment of Th1-mediated autoimmune diseases, such as multiple sclerosis.

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