CD40-targeted Adenoviral Cancer Vaccines: the Long and Winding Road to the Clinic

Overview

Journal J Gene Med

Specialties Genetics
Molecular Biology

Date 2012 Jan 10

PMID 22228547

Citations 13

Authors

Basav N Hangalapura

Laura Timares

Dinja Oosterhoff

Rik J Scheper

David T Curiel

Tanja D de Gruijl

Affiliations

Soon will be listed here.

Abstract

The ability of dendritic cells (DCs) to orchestrate innate and adaptive immune responses has been exploited to develop potent anti-cancer immunotherapies. Recent clinical trials exploring the efficacy of ex vivo modified autologous DC-based vaccines have reported some promising results. However, in vitro generation of autologous DCs for clinical administration, their loading with tumor associated antigens (TAAs) and their activation, is laborious and expensive, and, as a result of inter-individual variability in the personalized vaccines, remains poorly standardized. An attractive alternative approach is to load resident DCs in vivo by targeted delivery of TAAs, using viral vectors and activating them simultaneously. To this end, we have constructed genetically-modified adenoviral (Ad) vectors and bispecific adaptor molecules to retarget Ad vectors encoding TAAs to the CD40 receptor on DCs. Pre-clinical human and murine studies conducted so far have clearly demonstrated the suitability of a 'two-component' (i.e. Ad and adaptor molecule) configuration for targeted modification of DCs in vivo for cancer immunotherapy. This review summarizes recent progress in the development of CD40-targeted Ad-based cancer vaccines and highlights pre-clinical issues in the clinical translation of this approach.

Citing Articles

A pseudotyped adenovirus serotype 5 vector with serotype 49 fiber knob is an effective vector for vaccine and gene therapy applications.

Bliss C, Hulin-Curtis S, Williams M, Maruskova M, Davies J, Statkute E Mol Ther Methods Clin Dev. 2024; 32(3):101308.

PMID: 39206304 PMC: 11357811. DOI: 10.1016/j.omtm.2024.101308.

Engineering a Novel Modular Adenoviral mRNA Delivery Platform Based on Tag/Catcher Bioconjugation.

Geng K, Rice-Boucher P, Kashentseva E, Dmitriev I, Lu Z, Goedegebuure S Viruses. 2023; 15(11).

PMID: 38005953 PMC: 10674448. DOI: 10.3390/v15112277.

Sendai virus-based immunoadjuvant in hydrogel vaccine intensity-modulated dendritic cells activation for suppressing tumorigenesis.

Zheng B, Peng W, Gan L, Guo M, Wang S, Zhang X Bioact Mater. 2021; 6(11):3879-3891.

PMID: 33937591 PMC: 8076650. DOI: 10.1016/j.bioactmat.2021.04.002.

Retargeting adenoviruses for therapeutic applications and vaccines.

Barry M, Rubin J, Lu S FEBS Lett. 2020; 594(12):1918-1946.

PMID: 31944286 PMC: 7311308. DOI: 10.1002/1873-3468.13731.

Constitutively active GSK3β as a means to bolster dendritic cell functionality in the face of tumour-mediated immune suppression.

Lopez Gonzalez M, Oosterhoff D, Lindenberg J, Milenova I, Lougheed S, Martianez T Oncoimmunology. 2019; 8(10):e1631119.

PMID: 31646076 PMC: 6791458. DOI: 10.1080/2162402X.2019.1631119.

References

Pincha M, Sundarasetty B, Stripecke R . Lentiviral vectors for immunization: an inflammatory field. Expert Rev Vaccines. 2010; 9(3):309-21. DOI: 10.1586/erv.10.9. View

Harrop R, John J, Carroll M . Recombinant viral vectors: cancer vaccines. Adv Drug Deliv Rev. 2006; 58(8):931-47. DOI: 10.1016/j.addr.2006.05.005. View

Granelli-Piperno A, Pritsker A, Pack M, Shimeliovich I, Arrighi J, Park C . Dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin/CD209 is abundant on macrophages in the normal human lymph node and is not required for dendritic cell stimulation of the mixed leukocyte reaction. J Immunol. 2005; 175(7):4265-73. PMC: 1378112. DOI: 10.4049/jimmunol.175.7.4265. View

Xiang Z, Yang Y, Wilson J, Ertl H . A replication-defective human adenovirus recombinant serves as a highly efficacious vaccine carrier. Virology. 1996; 219(1):220-7. DOI: 10.1006/viro.1996.0239. View

Denfeld R, Hollenbaugh D, Fehrenbach A, Weiss J, von Leoprechting A, Mai B . CD40 is functionally expressed on human keratinocytes. Eur J Immunol. 1996; 26(10):2329-34. DOI: 10.1002/eji.1830261009. View

Belousova N, Krendelchtchikova V, Curiel D, Krasnykh V . Modulation of adenovirus vector tropism via incorporation of polypeptide ligands into the fiber protein. J Virol. 2002; 76(17):8621-31. PMC: 136983. DOI: 10.1128/jvi.76.17.8621-8631.2002. View

Huang D, Pereboev A, Korokhov N, He R, Larocque L, Gravel C . Significant alterations of biodistribution and immune responses in Balb/c mice administered with adenovirus targeted to CD40(+) cells. Gene Ther. 2007; 15(4):298-308. PMC: 7091597. DOI: 10.1038/sj.gt.3303085. View

Hangalapura B, Oosterhoff D, Gupta T, de Groot J, Wijnands P, van Beusechem V . Delivery route, MyD88 signaling and cross-priming events determine the anti-tumor efficacy of an adenovirus based melanoma vaccine. Vaccine. 2011; 29(12):2313-21. PMC: 3058128. DOI: 10.1016/j.vaccine.2011.01.022. View

Steinman R . Dendritic cells in vivo: a key target for a new vaccine science. Immunity. 2008; 29(3):319-24. DOI: 10.1016/j.immuni.2008.08.001. View

10.

Ueno H, Palucka A, Banchereau J . The expanding family of dendritic cell subsets. Nat Biotechnol. 2010; 28(8):813-5. DOI: 10.1038/nbt0810-813. View

11.

Oosterhoff D, Sluijter B, Hangalapura B, de Gruijl T . The dermis as a portal for dendritic cell-targeted immunotherapy of cutaneous melanoma. Curr Top Microbiol Immunol. 2011; 351:181-220. DOI: 10.1007/82_2011_136. View

12.

Zabner J, Petersen D, Puga A, Graham S, Couture L, Keyes L . Safety and efficacy of repetitive adenovirus-mediated transfer of CFTR cDNA to airway epithelia of primates and cotton rats. Nat Genet. 1994; 6(1):75-83. DOI: 10.1038/ng0194-75. View

13.

Thacker E, Nakayama M, Smith B, Bird R, Muminova Z, Strong T . A genetically engineered adenovirus vector targeted to CD40 mediates transduction of canine dendritic cells and promotes antigen-specific immune responses in vivo. Vaccine. 2009; 27(50):7116-24. PMC: 2784276. DOI: 10.1016/j.vaccine.2009.09.055. View

14.

Thacker E, Timares L, Matthews Q . Strategies to overcome host immunity to adenovirus vectors in vaccine development. Expert Rev Vaccines. 2009; 8(6):761-77. PMC: 3700409. DOI: 10.1586/erv.09.29. View

15.

Wei H, Wang S, Zhang D, Hou S, Qian W, Li B . Targeted delivery of tumor antigens to activated dendritic cells via CD11c molecules induces potent antitumor immunity in mice. Clin Cancer Res. 2009; 15(14):4612-21. DOI: 10.1158/1078-0432.CCR-08-3321. View

16.

Brave A, Ljungberg K, Wahren B, Liu M . Vaccine delivery methods using viral vectors. Mol Pharm. 2007; 4(1):18-32. DOI: 10.1021/mp060098+. View

17.

Tacken P, de Vries I, Torensma R, Figdor C . Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting. Nat Rev Immunol. 2007; 7(10):790-802. DOI: 10.1038/nri2173. View

18.

Tillman B, de Gruijl T, Luykx-de Bakker S, Scheper R, Pinedo H, Curiel T . Maturation of dendritic cells accompanies high-efficiency gene transfer by a CD40-targeted adenoviral vector. J Immunol. 1999; 162(11):6378-83. View

19.

Campos S, Barry M . Current advances and future challenges in Adenoviral vector biology and targeting. Curr Gene Ther. 2007; 7(3):189-204. PMC: 2244792. DOI: 10.2174/156652307780859062. View

20.

Butterfield L, Comin-Anduix B, Vujanovic L, Lee Y, Dissette V, Yang J . Adenovirus MART-1-engineered autologous dendritic cell vaccine for metastatic melanoma. J Immunother. 2008; 31(3):294-309. PMC: 3651040. DOI: 10.1097/CJI.0b013e31816a8910. View