scholarly journals Neoantigen Dendritic Cell Vaccination Combined with Anti-CD38 and CpG Elicits Anti-Tumor Immunity against the Immune Checkpoint Therapy-Resistant Murine Lung Cancer Cell Line LLC1

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5508
Author(s):  
Changbo Sun ◽  
Koji Nagaoka ◽  
Yukari Kobayashi ◽  
Hidewaki Nakagawa ◽  
Kazuhiro Kakimi ◽  
...  

An important factor associated with primary resistance to immune-checkpoint therapies (ICT) is a “cold” tumor microenvironment (TME), characterized by the absence of T cell infiltration and a non-inflammatory milieu. Whole-exome and RNA sequencing to predict neoantigen expression was performed on the LLC1 cell line which forms “cold” tumors in mice. Dendritic cell (DC)-based vaccination strategies were developed using candidate neoantigen long peptides (LPs). A total of 2536 missense mutations were identified in LLC1 and of 132 candidate neoantigen short peptides, 25 were found to induce CD8+ T cell responses. However, they failed to inhibit LLC1 growth when incorporated into a cancer vaccine. In contrast, DCs pulsed with LPs induced CD4+ and CD8+ T cell responses and one of them, designated L82, delayed LLC1 growth in vivo. By RNA-Seq, CD38 was highly expressed by LLC1 tumor cells and, therefore, anti-CD38 antibody treatment was combined with L82-pulsed DC vaccination. This combination effectively suppressed tumor growth via a mechanism relying on decreased regulatory T cells in the tumor. This study demonstrated that an appropriate vaccination strategy combining neoantigen peptide-pulsed DC with anti-CD38 antibody can render an ICT-resistant “cold” tumor susceptible to immune rejection via a mechanism involving neutralization of regulatory T cells.

2005 ◽  
Vol 174 (6) ◽  
pp. 3344-3351 ◽  
Author(s):  
S. M. Mansour Haeryfar ◽  
Richard J. DiPaolo ◽  
David C. Tscharke ◽  
Jack R. Bennink ◽  
Jonathan W. Yewdell

2012 ◽  
Vol 7 (S1) ◽  
Author(s):  
Lauren Lepone ◽  
Giovanna Rappocciolo ◽  
Paolo Piazza ◽  
Mariel Jais ◽  
Frank J Jenkins ◽  
...  

Science ◽  
2012 ◽  
Vol 338 (6106) ◽  
pp. 532-536 ◽  
Author(s):  
L. Pace ◽  
A. Tempez ◽  
C. Arnold-Schrauf ◽  
F. Lemaitre ◽  
P. Bousso ◽  
...  

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