Reinvigoration of innate and adaptive immunity via therapeutic cellular vaccine for patients with AML

Fujii, Shin‐ichiro; Kawamata, Toyotaka; Shimizu, Kazuo; Nakabayashi, Jun; Yamasaki, Satoshi; Iyoda, Tomonori; Shinga, Jun; Nakazato, Hiroshi; Sanpei, An; Kawamura, Masami; Ueda, Shogo; Dörrie, Jan; Mojsov, Svetlana; Dhodapkar, Madhav V.; Hidaka, Masaaki; Nojima, Masanori; Nagamura, Fumitaka; Yoshida, Shigemi; Goto, Toshio; Tojo, Arinobu

doi:10.1016/j.omto.2022.09.001

Cited by 12 publications

(10 citation statements)

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“…According to concerns for patients who have the low frequency of iNKT cells, several groups demonstrated that NK cell response was shown after α-GalCer-pulsed DC therapy ( 24 , 26 , 37 , 48 ). Particularly, an initial study showed that NK cell response depends on the function of iNKT cells, but not the frequency.…”

Section: Discussionmentioning

confidence: 99%

“…However, we did not observe a similar response in T cells. Recently, we conducted a phase I trial involving aAVC-expressing WT1 therapy targeted at patients with relapsed and refractory AML ( 37 ). Our results revealed that either iNKT or NK cells or both were activated in all the patients, even in patients with lung cancer and relapse and refractory AML, including those with low counts of iNKT cells.…”

Section: Discussionmentioning

confidence: 99%

“…The in vivo DCs in the lungs, liver, and spleen that captured aAVCs undergo maturation via interaction with iNKT cells, which is brought about by CD40L/CD40 interactions and inflammatory cytokines (IFN-γ and TNF-α) ( 27 – 29 , 32 , 33 ). aAVC therapy is a cellular therapy platform, and we demonstrated that many types of antigens were used, such as OVA, MART-1, NY-ESO-1, and WT1 antigens in murine models ( 27 – 29 , 34 – 36 ) and also against human relapsed and refractory acute myelogenous leukemia patients ( 37 ). Such in vivo DC-targeting therapies promote CD8 + T cell responses more effectively than ex vivo DC therapies ( 28 , 32 , 33 , 38 ).…”

Section: Introductionmentioning

confidence: 99%

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Tumor epitope spreading by a novel multivalent therapeutic cellular vaccine targeting cancer antigens to invariant NKT-triggered dendritic cells in situ

Yamasaki,

Shimizu,

Fujii

2024

Front. Immunol.

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IntroductionCancer is categorized into two types based on the microenvironment: cold and hot tumors. The former is challenging to stimulate through immunity. The immunogenicity of cancer relies on the quality and quantity of cancer antigens, whether recognized by T cells or not. Successful cancer immunotherapy hinges on the cancer cell type, antigenicity and subsequent immune reactions. The T cell response is particularly crucial for secondary epitope spreading, although the factors affecting these mechanisms remain unknown. Prostate cancer often becomes resistant to standard therapy despite identifying several antigens, placing it among immunologically cold tumors. We aim to leverage prostate cancer antigens to investigate the potential induction of epitope spreading in cold tumors. This study specifically focuses on identifying factors involved in secondary epitope spreading based on artificial adjuvant vector cell (aAVC) therapy, a method established as invariant natural killer T (iNKT) -licensed DC therapy.MethodsWe concentrated on three prostate cancer antigens (prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostatic acid phosphatase (PAP)). By introducing allogeneic cells with the antigen and murine CD1d mRNA, followed by α-galactosylceramide (α-GalCer) loading, we generated five types of aAVCs, i.e, monovalent, divalent and trivalent antigen-expressing aAVCs and four types of prostate antigen-expressing cold tumors. We evaluated iNKT activation and antigen-specific CD8+ T cell responses against tumor cells prompted by the aAVCs.ResultsOur study revealed that monovalent aAVCs, expressing a single prostate antigen, primed T cells for primary tumor antigens and also induced T cells targeting additional tumor antigens by triggering a tumor antigen-spreading response. When we investigated the immune response by trivalent aAVC (aAVC-PROS), aAVC-PROS therapy elicited multiple antigen-specific CD8+ T cells simultaneously. These CD8+ T cells exhibited both preventive and therapeutic effects against tumor progression.ConclusionsThe findings from this study highlight the promising role of tumor antigen-expressing aAVCs, in inducing efficient epitope spreading and generating robust immune responses against cancer. Our results also propose that multivalent antigen-expressing aAVCs present a promising therapeutic option and could be a more comprehensive therapy for treating cold tumors like prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tumor epitope spreading by a novel multivalent therapeutic cellular vaccine targeting cancer antigens to invariant NKT-triggered dendritic cells in situ

Yamasaki,

Shimizu,

Fujii

2024

Front. Immunol.

Self Cite

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“…For immune-response groups, it will be necessary to improve vaccines to induce earlier responses. For immunocompromised groups, passive immunotherapy, targeting immune suppression or a new kind of WT1 vaccine should be developed [ 18 ]. Since immunoreactivity does not correlate with AML classification or age, predicting such reactivity presents a new challenge.…”

Section: Discussionmentioning

confidence: 99%

Immunoreactivity to WT1 peptide vaccine is associated with prognosis in elderly patients with acute myeloid leukemia: follow-up study of randomized phase II trial of OCV-501, an HLA class II-binding WT1 polypeptide

Naoe

Saito

Hosono

et al. 2023

Cancer Immunol Immunother

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We previously conducted a randomized phase II trial of OCV-501, a WT1 peptide presented by helper T cells, in elderly AML (acute myeloid leukemia) patients in first remission, indicating no difference in 2-year disease-free survival (DSF) between the OCV-501 and placebo groups. Here, we analyzed 5-year outcome and biomarkers. Five-year DFS was 36.0% in the OCV-501 group (N = 52) and 33.7% in the placebo group (N = 53), with no significant difference (p = 0.74). The peripheral WT1 mRNA levels were marginally suppressed in the OCV-501 group compared with the placebo group. Enhanced anti-OCV-501 IgG response by the 25th week was an independent favorable prognostic factor. Anti-OCV-501 IFNγ responses were less frequent than the IgG reactions. These findings suggest that host immunoreactivity has a significant impact on the prognosis of AML and that further improvement of the WT1 peptide vaccine is needed.

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“…Moreover, aAVC-CoV-2 induced higher numbers of long-term memory CTLs [96]. In a phase I trial against cancer, we have just reported the induction of innate and adaptive immunity in addition to safety in refractory and relapse AML patients using a WT1 mRNA-expressing aAVC [100]. It could be developed for viral protection in humans.…”

Section: Development Of a New Type Of T Cell Targeting Vaccinementioning

confidence: 99%

Association of cellular immunity with severity of COVID-19 from the perspective of antigen-specific memory T cell responses and cross-reactivity

et al. 2022

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Coronaviruses regularly cause outbreaks of zoonotic diseases characterized by severe pneumonia. The new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused the global pandemic disease COVID-19 that began at the end of 2019 and spread rapidly owing to its infectious nature and rapidly progressing pneumonia. Although the infectivity of SARS-CoV-2 is high, indicated by the worldwide spread of the disease in a very short period, many individuals displayed only subclinical infection, and some of them transmitted the disease to individuals who then developed a severe symptomatic infection. Furthermore, there are differences in the severity of infection across countries, which can be attributed to factors such as the emergence of viral mutations in a short period of time as well as to the immune responses to viral factors. Anti-viral immunity generally consists of neutralizing antibodies that block viral infection and cytotoxic CD8+ T cells that eliminate the virus-infected cells. There is compelling evidence for the role of neutralizing antibodies in protective immunity in SARS-CoV-2 infection. However, the role of CD4+ and CD8+ T cells after the viral entry is complex and warrants a comprehensive discussion. Here, we discuss the protection afforded by cellular immunity against initial infection and development of severe disease. The initial failure of cellular immunity to control the infection worsens the clinical outcomes and functional profiles that inflict tissue damage without effectively eliminating viral reservoirs, while robust T cell responses are associated with mild outcomes. We also discuss persistent long-lasting memory T cell-mediated protection after infection or vaccination, which is rather complicated as it may involve SARS-CoV-2-specific cytotoxic T lymphocytes or cross-reactivity with previously infected seasonal coronaviruses, which are largely related to HLA genotypes. In addition, cross-reactivity with mutant strains is also discussed. Lastly, we discuss appropriate measures to be taken against the disease for immunocompromised patients. In conclusion, we provide evidence and discuss the causal relationship between natural infection- or vaccine-mediated memory T cell immunity and severity of COVID-19. This review is expected to provide a basis to develop strategies for the next generation of T cell-focused vaccines and aid in ending the current pandemic.

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Reinvigoration of innate and adaptive immunity via therapeutic cellular vaccine for patients with AML

Cited by 12 publications

References 50 publications

Tumor epitope spreading by a novel multivalent therapeutic cellular vaccine targeting cancer antigens to invariant NKT-triggered dendritic cells in situ

Tumor epitope spreading by a novel multivalent therapeutic cellular vaccine targeting cancer antigens to invariant NKT-triggered dendritic cells in situ

Immunoreactivity to WT1 peptide vaccine is associated with prognosis in elderly patients with acute myeloid leukemia: follow-up study of randomized phase II trial of OCV-501, an HLA class II-binding WT1 polypeptide

Association of cellular immunity with severity of COVID-19 from the perspective of antigen-specific memory T cell responses and cross-reactivity

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