Expanding the Reach of Monoclonal Antibodies: A Review of Synthetic Nucleic Acid Delivery in Immunotherapy
Abstract
:1. Introduction
2. Monoclonal Antibodies: From Hybridoma to Humanized Transgenic Mice
3. Challenges of Making Monoclonal Antibody Therapies More Accessible: Current Limitations and Future Directions
4. Approaches for Monoclonal Antibody Delivery: A Promising Alternative for Increased Accessibility and Efficiency
5. Different Delivery Platforms for Monoclonal Antibodies
AAV-Based Delivery | ||||
---|---|---|---|---|
Encoded mAb(s) | Modifications | Experimental Model | Mode of Delivery | Reference |
anti-HIV-1 gp160 (IgG1b12) | dual promoter (pCMV/HC/EF1a/LC) | Rag1 mice | rAAV, IM | [32] |
anti-human EGFR (14E1 and 14E1A, ablated CDR3) | nu/nu mice | AAV2/1, IM | [142] | |
anti-HIV gp41 (4E10) and anti-HIV gp120 (b12) | Rag2−/−γc−/−, NSG, B6, Balb/C | AAV2/8, IM | [7] | |
anti-Aβ | C57BL/6 mice | AAV1, IM | [29] | |
anti-ganglioside GM3(Neu5Gc) (14F7, mouse IgG1) | BALB/c mice | AAV2/9, IM, IV | [143] | |
anti-METH | scFv, self-complementary AAV | BALB/c mice | AAV8, IV | [30] |
anti-HIV-1 gp41 (10E8), anti-HIV-1 gp120 (3BNC117, 10-1074) | “LS mutation” (M428L (Leucine)/N434S (Serine)) to increase half-life, vectors included specific miRNAs to promote transcriptional cleavage of transgene’s mRNA in APCs | rhesus macaques | AAV1, IM | [27] |
anti-SIV gp120 and gp140 (5L7) | Mamu B*08-neg B*17-neg female Indian-origin rhesus macaque | AAV1, IM | [24] | |
anti-PD-1 (Nb11) | nanobody (VHH) | C57BL/6 mice | AAV8, IV | [28] |
anti-EBOV GP2 internal fusion loop (CA45) | F129L, Y445F, and Y731F mutations in the AAV6 capsid | BALB/c mice | AAV6.2FF, IM | [25] |
anti-MARV GP (MR78, MR82 and MR191) | bicistronic, CASI promoter | BALB/c mice, Dorset lambs | AAV6.2FF, IM | [144] |
DNA-Based Delivery | ||||
Encoded mAb(s) | Modifications | Experimental Model | Mode of Delivery | Reference |
anti-human thyroglobulin | tet-off, tet-on | C57BL/6 mice, C3H mice | IM + EP | [63] |
anti-I-Ed, anti-IgDa, anti-NIP | C57BL/6 mice, BALB/c mice, BALB.B mice, C.B-17 mice | IM + EP | [64] | |
anti-HIV Env (VRC01) | BALB/c mice | IM + EP | [65] | |
anti-DENV nAb | LALA mutation | Foxn1/NuJ mice | IM + EP | [72] |
anti-CHIKV envelope | B6.Cg-Foxn1nu/J mice | IM + EP | [74] | |
anti-HER2 | modification of VL sequence by replacing asparagine at amino acid 65 with serine to remove potential N-glycosylation site | BALB/c mice | IM + EP | [145] |
anti-Influenza (A and B) | BALB/c and CAnN.Cg-Foxn1Nu | IM + EP with hyaluronidase pretreatment | [71] | |
anti-PSMA | B6.Cg-Foxn1 nu/J and C57BL/6J mice | IM + EP | [75] | |
anti-CD4, anti-influenza, anti-Ebola | BALB/c mice | IM + EP, IM + EP with hyaluronidase pretx | [146] | |
anti-Zaire ebolavirus glycoprotein | modification of N terminus amino acids back to germline | BALB/c (anti-CD4 and anti-CD8 transient depletion) | IM + EP with hyaluronidase | [68] |
anti-CTLA-4 | Sequence modifications based on sequence alignment to the mouse germline sequence | C57Bl/6, BALB/c (anti-CD4 and anti-CD8 transient depletion) | IM + EP with hyaluronidase | [147] |
anti-HER2 | BALB/c, athymic nude, RAG2−/−gc−/− | IM + EP with hyaluronidase pretx | [73] | |
anti-ZIKV E protein DIII domain (DMAb-ZK190) | LALA mutation | C57BL/6 mice, Rhesus macaques | IM + EP with hyaluronidase pretreatment in mice, IM + EP only in rhesus macaques | [77] |
anti-OspA Lyme | framework modification of the WT variant | C3H mice | IM + EP with hyaluronidase | [148] |
anti-PCSK9 | C57BL/6J wild-type and nude B6.Cg-foxn1nu/J mice | IM + EP | [149] | |
anti-HER2 | Nu/J mice | IM + EP with hyaluronidase | [78] | |
anti-PD-1 | BALB/c mice | IM + EP | [150] | |
anti-human CEA, anti-human EGFR, anti-HER2 | Swifter sheep, C57BL/6J RAG1 ko mice | IM + EP with hyaluronidase pretx | [151] | |
multiple HIV-1-specific bNAbs | modification of the C- and N-terminus of the variable region to germline | BALB/c (anti-CD4 and anti-CD8 transient depletion), Rhesus macaques | IM + EP with hyaluronidase | [79] |
anti-HBV | athymic nude CAnN.Cg-Foxn1nu/Crl mice | IM + EP | [152] | |
anti-mCTLA-4 (9D9), anti-ratPD-1 | C57BL/6J mice | IM + EP with hyaluronidase pretx | [153] | |
Intratumoral + EP | ||||
anti-ZIKV envelope | B6.Cg-Foxn1nu/J mice | IM + EP | [154] | |
2C7, directed against a lipooligosaccharide glycan epitope, Neisseria gonorrhoeae | two complement enhancing variants, HC_E430G and HC_E345K, one complement abrogating variant HC_K322A/D270A | Jh mice, nude mice | IM + EP with hyaluronidase | [155] |
anti-HER2 | BALB/c mice | IM + EP with hyaluronidase pretx | [156] | |
anti-SARS-CoV2 spike | L234F/L235E/P331S; “TM” to ablate FcR and C1q binding, M252Y/S254T/T256E; “YTE” to promote FcRn-mediated recycling | BALB/c | IM + EP with hyaluronidase | [70] |
mAb clones CIS43, 317, and L9, which target a junctional epitope, major repeat, and minor repeat of the Plasmodium falciparum circumsporozoite protein (CSP), respectively | reverting specific, non-essential residues in the framework region back to germline configuration | BALB/cJ (anti-CD4 and anti-CD8 transient depletion) | IM + EP with hyaluronidase | [69] |
anti-human CEA | Swifter sheep | IM + EP with hyaluronidase | [157] | |
mRNA-Based delivery | ||||
Encoded mAb(s) | Modifications | Experimental Model | Mode of Delivery | Reference |
anti-CD3/anti-claudin 6 (CLDN6), anti-CD3/anti-caludin 18.2 (CLDN18.2), anti-CD3/anti-epithelial cell adhesion molecule (EpCAM), anti-CD3/(anti-CLDN6)2 | 1-methylpseudouridine | NOD.Cg-Prkdscid IL2rgtm1Wjl/SzJ (NSG) mice | Formulation with TransIT-mRNA Transfection kit, IV | [99] |
anti-HIV Env (VRC01) | 1-methylpseudouridine | BALB/c mice | LNP, IV | [97] |
anti-Rabies glycoprotein G, anti-Botulinum neurotoxin serotype A (VHH-based neutralizing agent, VNA), anti-CD20, anti-HIV gp120, anti-Influenza B HA, anti-Shiga toxin 2 (VNA) | two fused VHHs complemented by an albumin-binding peptide | Swiss-Albino mice (rabies and influenza b) CD1 mice (VNAs) | LNP, IV | [100] |
anti-Influenza A | 1-methylpseudouridine | cynomolgus monkeys | LNP, IV | [98] |
anti-CHIKV E2 glycoprotein (CHIKV-24) | cynomolgus monkeys | LNP, IV | [95] | |
anti-HER2 | C57BL/6 mice | cKK-E12 (also known as MD-1) lipid-like nanoparticles, IV | [127] | |
Anti-ZIKV Env (ZIKV-117) | alphavirus replicon (replicating viral RNA that amplifies) 1-methylpseudouridine | C57BL/6 mice | Nanostructured lipid carrier, IM | [129] |
anti-HIV GP120 (PGT121) | 1-methylpseudouridine | female Katahdin ewes | aerosol delivery of unformulated mRNA in water | [96] |
anti-Influenza A matrix protein 2/anti-mouse Fcγ receptor IV | 1-methylpseudouridine | DOTAP (1,2-dioleoyl-3-trimethylammonium-propane)/cholesterol nanoparticles delivered intratracheally | [158] | |
anti-CHIKV Env (mRNA-1944) | human | LNP, IV | [126] | |
Poxviruses: Mature virion, c7D11 (anti-L1); Enveloped virion, c8A (anti-B5) and c6C (anti-A33) | New Zealand White rabbits | LNP, IM jet injection | [159] | |
anti-PD-1 | 1-methylpseudouridine | C57BL/6 mice | LNP, IV | [128] |
anti-SARS-CoV-2 | LS mutation (M428L/N434S) and GPI anchor 1-methylpseudouridine | Golden Syrian hamster | poly-beta amino thio ester (PBATE), nebulizer | [133] |
6. Summary and Conclusions
7. Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mode of mAb Delivery | Advantages | Disadvantages |
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Adeno-Associated Virus (AAV) |
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Deoxyribonucleic Acid (DNA) |
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Messenger RNA (mRNA) |
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Chung, C.; Kudchodkar, S.B.; Chung, C.N.; Park, Y.K.; Xu, Z.; Pardi, N.; Abdel-Mohsen, M.; Muthumani, K. Expanding the Reach of Monoclonal Antibodies: A Review of Synthetic Nucleic Acid Delivery in Immunotherapy. Antibodies 2023, 12, 46. https://doi.org/10.3390/antib12030046
Chung C, Kudchodkar SB, Chung CN, Park YK, Xu Z, Pardi N, Abdel-Mohsen M, Muthumani K. Expanding the Reach of Monoclonal Antibodies: A Review of Synthetic Nucleic Acid Delivery in Immunotherapy. Antibodies. 2023; 12(3):46. https://doi.org/10.3390/antib12030046
Chicago/Turabian StyleChung, Christopher, Sagar B. Kudchodkar, Curtis N. Chung, Young K. Park, Ziyang Xu, Norbert Pardi, Mohamed Abdel-Mohsen, and Kar Muthumani. 2023. "Expanding the Reach of Monoclonal Antibodies: A Review of Synthetic Nucleic Acid Delivery in Immunotherapy" Antibodies 12, no. 3: 46. https://doi.org/10.3390/antib12030046