Table 1.1.
Examples of nanomedicines for B cell targeting.
| Mechanisms | Targets | Diseases/Applications | Clinical Options | Targeting Moieties | Nano-strategies |
|---|---|---|---|---|---|
| Direct B cell depletion | CD20 | Non-Hodgkin’s lymphoma (NHL) [105–107, 114, 115, 120], chronic lymphocytic leukemia (CLL) [110, 111], rheumatoid arthritis (RA) [109], leukemia [125], melanoma [126], etc | mAb: rituximab (Rituxan®), obinutuzumab (Gazyva®), ofatumumab (Kesimpta®), ibritumomab (Zevalin®), ocrelizumab (Ocrevus®), etc. More details in [288]. | Antibodies [92–104], Fab’ fragment [105–115, 120], scFv [122, 124, 125], aptamers [126] | PLA-b-PEG-COOH, PCL-COOH [93, 94], PLGA [95], caveosphere [96], albumin [97], chitosan/quantum dots [98], liposome [99, 100, 126], micelles [101], iron oxide [102–104], PHPMA [105–111], HSA [114, 115, 120], ELP [122], polystyrene-PEG-biotin [124], PEG-coated iron oxide [125] |
| CD19 | Burkitt’s lymphoma [130], acute lymphoblastic leukemia (ALL) [131–133, 135], rheumatoid arthritis [289] | mAb: inebilizumab (Uplizna®); BiTE: blinatumomab (Blincyto®); CAR-T therapies: axicabtagene ciloleucel (Yescarta®), tisagenlecleucel (Kymriah®), lisocabtagene maraleucel (Breyanzi®). More details in [290]. | Antibodies [130–132, 135, 137, 140, 289], CD19L [136] | Liposome [130, 132, 133], gold NPs [131], PEG-PCL [135], mPEG-bPEI-PEBP [137], iron oxide [140] | |
| CD22 | ALL [150], NHL [151], diffuse large B-cell lymphoma (DLBCL) [153] |
mAb: epratuzumab in clinical trials [291, 292]; ADC: inotuzumab ozogamicin (Besponsa®) [293]; CAR-T therapy: moxetumomab pasudotox (Lumoxiti®) [294] |
Antibodies [150, 151], Fab’ fragment [152], sialic acid [153], N-linked glycan scaffold [154] | Iron oxide [150], quantum dot [151], liposome [152], ChNP [153] | |
| CD38 | Multiple myeloma [157, 158] | mAb: daratumumab (Darzalex®); isatuximab-irfc (Sarclisa®) [155]. | Antibody [157, 158] | Chitosan NP [157], PEO-b-PBCL NP [158] | |
| Surface antigen signaling lymphocytic activation molecule-F7 | Multiple myeloma [161, 223] | mAb: elotuzumab (Empliciti®) [162] | Antibody [161, 223] | Silica/Gd NP [223] | |
| Idiotypic sequences | NHL [168, 169] | DNA vaccines failed several clinical trials [166, 167] | Immunogenic self-antigen expressing plasmid DNA [168, 169] | PEI-PLGA NP [168, 169] | |
| Scavenger receptor type B-1 | DLBCL [170] | N/A | Cholesterol-poor high-density lipoprotein [170] | Lipoprotein-like NP [170] | |
| Modulation of B cell receptor signaling | CD79a/b | NHL [179, 180], RA [182] | ADC: polatuzumab vedotin (Polivy®) [181] | Antibody [179, 180, 182] | N/A |
| Bruton tyrosine kinase | CLL, mantle cell lymphoma, small lymphocytic lymphoma, marginal zone lymphoma, RA [187] | Kinase inhibitors: ibrutinib (Imbruvica®), acalabrutinib (Calquence®), zanubrutinib (Brukinsa®) [295] | Inhibitor (Ibrutinib) [186], siRNA [187] | Chitosan/sulfobutylether-b-cyclodextrin NP [185], PEG-b-PLGA [187] | |
| Spleen tyrosine kinase | ALL [191], mantel cell lymphoma [192], B-precursor acute lymphoblastic leukemia [193], RA [296], CLL [297] | Kinase inhibitor: fostamatinib (Tavalisse®); entospletinib in clinical trials Phase I/II [189] | Inhibitors (C61 [191–193], R406 and R788 [296, 297]) | Liposome [191–193] | |
| Phosphoinositide 3 kinase | Pancreatic adenocarcinoma [200], breast cancer [201, 207], multiple myeloma [208], etc | Kinase inhibitor: alpelisib (Piqray®), idelalisib (Zydelig®), copanlisib (Aliqupa®), duvelisib (Copiktra®), umbralisib (Ukoniq®). More information provided in [298]. | Inhibitors (IPI-549 [200, 201], GDC-0941 [206], AS101 [207], Walterinnesia aegyptia venom [207, 208]) | PLGA [200], PEGylated PCL NP [201], silica NP [207, 208] | |
| Targeting B cell survival | B cell maturation antigen (BCMA) | Multiple myeloma [222, 223] |
ADC: belantamab mafodotin (Blenrep®); CAR T therapy: idecabtagene vicleucel (Abecma®). More in [299]. |
BiTE, CAR-T, BCMA72–80 peptide [222], antibody [223] | PLGA NP [222], silica/Gd NP [223] |
| B cell activating factor receptor (BAFF-R) | ALL [227], atherosclerosis [228], RA [230], NHL [231], myasthenia [232] |
mAb: belimumab (Benlysta®); tabalumab/bortezomib/ianalumab in clinical trials [217, 300]; CAR-T therapy PMB-101 got IND (investigational new drug) clearance for ALL. |
CAR-T [227], antibody [228, 229], CRISPR-Cas9 [230], BAFF competitor (mBAFF) [231], siRNA [232, 233], RNA aptamer [234] | (PEG-b-PLGA)-based cationic lipid-assisted NP [230], PEGylated liposome [231] | |
| Transmembrane activator and CAML interactor (TACI) | Systemic lupus erythematosus [235], RA [236], multiple myeloma [239–241] | Recombinant fusion proteins: atacicept failed in clinical trials [237]. More discussion in [242]. | TACI-Ig [235, 236], anti-APRIL antibody [239], CAR-T [240, 241] (usually combined with BCMA-targeting) | N/A | |
| Targeting B cell/T cell costimulation and immune checkpoint blockade | CD80/CD86 | RA [249], renal transplant [251] | Recombinant fusion proteins: abatacept (Orencia®); FPT155 in clinical trial Phase Ia/Ib [301]. | CTLA-Ig [249], antibody [251], ovalbumin (targeting dendritic cells) [252, 303, 304] | Liposome [302], carbon nanotube [303] |
| CD40 | RA [257], activate APCs [259], melanoma [260] | mAb: sotigalimab in clinical trials phase I/II. More discussion on CD40 targeting in [263]. | Antibody [257, 259, 260, 303] | Silicon NP [259], PLGA NP [260], carbon nanotube [303] | |
| Programmed cell death ligand 1 and 2 (PD-L1/L2) | Various type of tumors including melanoma [273], colorectal cancel [274], breast cancer [275, 278, 284], glioma [280], melanoma [283], DLBCL [286], etc. |
αPD-1 mAb: permbrolizumab (Keytruda®), nivolumab (Opdivo®), cemiplimab (Libtayo®); αPD-L1 mAb: atezolizumab (Tecentriq®), avelumab (Bavencio®), durvalumab (Imfinzi®), etc. More in [304]. |
Antibody [265–268, 272–274], peptide antagonist PPA [278, 280], scFv [282], plasmid DNA encoding CRISPR/Cas13a [283], siRNA [284, 285], microRNA [286] | PLGA NP [273], gold NP [274], liposome [275], PHPMA [278], PEG-PCL NP [280], iTEP [253], PEI-HPBA [254], lipid-coated calcium phosphate NP [284], lipid NP [286] |