Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

Goyvaerts, Cleo; Breckpot, Karine

doi:10.1155/2015/785634

Cited by 42 publications

(32 citation statements)

References 199 publications

(180 reference statements)

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“…Sipuleucel-T is a cancer therapeutic vaccine that targets patient specific tumor epitopes. The patients APCs are exposed to antigen prostatic acid phosphatase (95% expressed in prostate cancer), fusion protein and granulocyte-macrophage colony stimulation factor (GM-CSF) for the maturation of the APCs [179–181]. The patient’s matured and exposed APCs with tumor antigen recognition are then reinfused in the patients.…”

Section: Revisiting Anti-angiogenesismentioning

confidence: 99%

Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?

2017

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Angiogenesis is defined as the formation of new blood vessels from pre-existing vessels, and has been characterized as an essential process for tumor cell proliferation and viability. This has led to the development of pharmacological agents for anti-angiogenesis to disrupt the vascular supply and starve tumor of nutrients and oxygen, primarily through blockade of VEGF/VEGFR signaling. This effort has resulted in 11 anti-VEGF drugs approved for certain advanced cancers, alone or in combination with chemotherapy or other targeted therapies. But this success had only limited impact on overall survival of cancer patients, and rarely resulted in durable responses. Given the recent success of immunotherapies, combinations of anti-angiogenics with immune checkpoint blockers have become an attractive strategy. However, implementing such combinations will require a better mechanistic understanding of their interaction. Due to overexpression of pro-angiogenic factors in tumors, their vasculature is often tortuous and disorganized, with excessively branched leaky vessels. This enhances vascular permeability, which in turn is associated with high interstitial fluid pressure, and a reduction in blood perfusion and oxygenation. Judicious dosing of anti-angiogenic treatment can transiently normalize the tumor vasculature by decreasing vascular permeability and improving tumor perfusion and blood flow, and synergize with immunotherapy in this time-window. However, anti-angiogenics may excessively prune tumor vessels in a dose and time-dependent manner, which induces hypoxia and immunosuppression, including increased expression of the immune checkpoint programmed death receptor ligand (PD-L1). This review focuses on revisiting the concept of anti-angiogenesis in combination with immunotherapy as a strategy for cancer treatment.

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Section: Revisiting Anti-angiogenesismentioning

confidence: 99%

Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?

2017

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“…Consequently, strategies need to be developed that exclusively act on TiDCs, preferably on CD8a þ TiDCs, which are critical for the stimulation of antitumor immunity (8,9). Several strategies have been developed to target adjuvants like TLR ligands or IL12, together with antigens, to cross-priming DCs (10)(11)(12)(13)(14)(15). Often these exploit antibodies or nanobodies to surface markers differentially expressed by DC subsets (13,15).…”

Section: Introductionmentioning

confidence: 99%

“…Several strategies have been developed to target adjuvants like TLR ligands or IL12, together with antigens, to cross-priming DCs (10)(11)(12)(13)(14)(15). Often these exploit antibodies or nanobodies to surface markers differentially expressed by DC subsets (13,15). Such markers include C-type lectin receptors like DEC205 and DC-SIGN (11,12).…”

Section: Introductionmentioning

confidence: 99%

Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

Lint

Renmans

Broos

et al. 2016

Cancer Immunology Research

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“…In addition, heterologous immunization with a lentiviral vaccine and human adenovirus vector HAdV-5 expressing HIV-1 Gag, Pol, and Rev proteins resulted in superior immunogenicity and overcame pre-existing anti-HAdV-5 immunity 60 . While the majority of these experiments were performed with integrating lentiviral vectors pseudotyped with the envelope glycoprotein of vesicular stomatitis virus VSV-G, giving these vectors a broad tropism, recent developments have explored integration deficiency as an important safety feature and targeting of antigen-presenting cells as a means to modulate immune responses 61, 62…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Conserved Mosaics Delivered by Regimens with Integration-Deficient DC-Targeting Lentiviral Vector Induce Robust T Cells

et al. 2017

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To be effective against HIV type 1 (HIV-1), vaccine-induced T cells must selectively target epitopes, which are functionally conserved (present in the majority of currently circulating and reactivated HIV-1 strains) and, at the same time, beneficial (responses to which are associated with better clinical status and control of HIV-1 replication), and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising vaccine strategies; nevertheless, induction of robust long-term memory remains challenging. To this end, lentiviral vectors induce high frequencies of memory cells due to their low-inflammatory nature, while typically inducing only low anti-vector immune responses. Here, we describe construction of novel candidate vaccines ZVex.tHIVconsv1 and ZVex.tHIVconsv2, which are based on an integration-deficient lentiviral vector platform with preferential transduction of human dendritic cells and express a bivalent mosaic of conserved-region T cell immunogens with a high global HIV-1 match. Each of the two mosaic vaccines was individually immunogenic. When administered together in heterologous prime-boost regimens with chimpanzee adenovirus and/or poxvirus modified vaccinia virus Ankara (MVA) vaccines to BALB/c and outbred CD1-Swiss mice, they induced a median frequency of over 6,000 T cells/106 splenocytes, which were plurifunctional, broadly specific, and cross-reactive. These results support further development of this vaccine concept.

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Pros and Cons of Antigen-Presenting Cell Targeted Tumor Vaccines

Cited by 42 publications

References 199 publications

Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?

Anti-angiogenesis for cancer revisited: Is there a role for combinations with immunotherapy?

Intratumoral Delivery of TriMix mRNA Results in T-cell Activation by Cross-Presenting Dendritic Cells

HIV-1 Conserved Mosaics Delivered by Regimens with Integration-Deficient DC-Targeting Lentiviral Vector Induce Robust T Cells

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