Table. 2:
Recombinant BCG strains expressing cytokines, chemokines, tumor antigens or other non-mycobacterial antigens
| Name | Cytokine/Chemokine | Immune responses and safety | Therapeutic efficacy |
|---|---|---|---|
| 2A. Recombinant BCG strains expressing cytokines and chemokines. Some tested as cancer immunotherapeutic agents. | |||
| rBCG-IL4, rBCG-IL6, rBCG-GM-CSF, rBCG-IFN-γ, rBCG-rIL-2 | Secretory murine IL-4, IL-6, GM-CSF, IFN-γ and IL-2 | Increased cell-mediated immune response ex-vivo (murine splenocytes following restimulation) | No efficacy data (tumor model) |
| Murray et al., 1996 | |||
| PMID: 8570663 | |||
| rBCG-IL2 | Secretory murine IL-2 | Enhanced IFN-γ release ex-vivo (murine splenocytes following restimulation) | No efficacy data (tumor model) |
| O’Donnell et al., 1994 | |||
| PMID: 8188376 | |||
| rBCG-mIL-18 | Secretory murine IL-18 | Enhanced TH1 cytokine release ex-vivo (murine splenocytes following restimulation), macrophage toxicity against cancer cells | No efficacy data (tumor model) |
| Luo et al., 2004 | |||
| PMID: 15196240 | |||
| rBCG-IL-18 | Secretory murine IL-18 | Enhanced TH1 cytokine release ex-vivo (murine splenocytes following restimulation) | No efficacy data (tumor model) |
| Biet et al., 2002 | |||
| PMID: 12438324 | |||
| rBCG/IL-18 | Secretory murine IL-18 | Diminished IFN-γ release ex-vivo (murine splenocytes following restimulation) | No efficacy data (tumor model), reduced protective efficacy (mouse model of M. bovis infection) |
| Young et al., 2002 | |||
| PMID: 12067407 | |||
| rBCG/IL-2 | Secretory murine IL-2 | Enhanced IFN-γ release ex-vivo (murine splenocytes following restimulation) | No efficacy data (tumor model), reduced protective efficacy (mouse model of M. bovis infection) |
| Young et al., 2002 | |||
| PMID: 12067407 | |||
| BCG-IFN-γ | Secretory murine IFN-γ | No evidence | No efficacy data (tumor model) |
| Moreira et al., 2000 | |||
| PMID: 10968949 | |||
| rBCG (MCP3) | Secretory chemokine monocyte chemotactic protein 3 (MCP3) | Increased lymphocyte migration in vivo, increased T-cell responses and increased safety in SCID mice | No efficacy data (tumor model) Comparable protective efficacy against Mtb infection |
| Ryan et al., 2007 | |||
| PMID: 17074853 | |||
| rBCG(α-Ag-IL-2) | Secretory murine IL-2 | Increased IL-12 and IFN-γ secretion in peritoneal macrophages (C3H/HeN immunized mice), increased toxicity against urothelial cells | No efficacy data (tumor model) |
| Yamada et al., 2000 | |||
| PMID: 10893638 | |||
| rhIFN-α | Secretory human IFNα-2β | Increased release of IFN-γ and IP-10 in PBMCs post challenge | No efficacy data (tumor model) |
| Luo et al., 2001 | |||
| PMID: 11207657 | |||
| rBCG IFNα-2β | Secretory human IFNα-2β | Increased TH1 cytokine release, Increased cytotoxicity of PBMC against urothelial cells | No efficacy data (tumor model) |
| Fan and Han, 2007 | |||
| PMID: 24573929 | |||
| rBCG-IFNα | Secretory human IFNα-2β | Increased cytotoxicity of PBMC against urothelial cells via NKT and CD8+ T cells | No efficacy data (tumor model) |
| Liu et al., 2009 | |||
| PMID: 19214503 | |||
| rBCG-IFN-γ and rBCG-IL-2 | Secretory murine IFN-γ and IL-2 | Increased IL-2 and IL-4, enhanced CD4+T infiltration in vivo, increased tumor cytotoxicity | Prolonged animal survival and antitumor activity in MB49 orthotopic bladder cancer model |
| Arnold et al., 2014 | |||
| PMID: 14770083 | |||
| rBCG-IL-15 | Fusion protein expressing murine IL-15 and Mtb-Ag85B | Increased chemokine MIP2 and MIP1α | Prolonged animal survival, increased antitumor response driven by neutrophils and prolonged in MB49 orthotopic bladder cancer tumor model |
| Takeuchi et al., 2016 | |||
| Ref. 69. | |||
| PMID: 27093372 | |||
| 2B. Recombinant BCG strains expressing tumor antigens or other non-mycobacterial antigens. Some tested as cancer immunotherapeutic agents. | |||
| rBCG-S1PT | Genetically detoxified S1 subunit of pertussis toxin (S1PT) | Increased TNF- α and IL-10 | Prolonged animal survival and increased antitumor response and in MB49 orthotopic bladder tumor model |
| Andrade et al., 2010 | |||
| PMID: 19272796 | |||
| rBCG-S1+S1i | Genetically detoxified S1 subunit of pertussis toxin 9K/129G (rBCG-S1PT) | Increased polyfunctional CD4+ T cells | No efficacy data |
| Kanno et al., 2019 | |||
| PMID: 30941374 | |||
| rBCG 0148 and rBCG 2108 | Pneumococcal PspA-PdT fusion protein | Induced IL-17 α and IFN-γ production | No efficacy data (tumor model) |
| Goulart et al., 2017 | |||
| PMID: 28242071 | |||
| BCG-hIL2MUC1 | Truncated MUC1 and hIL-2 fusion protein | Increased CD8+ T cell infiltration in hu-PBL-SCID mouse model | Increased antitumor activity and survival (Breast Cancer model) |
| Chung et al., 2003 | |||
| PMID: 12649188 | |||
| BCG-disA-OE | Mtb disA diadenylate cyclase gene overexpressed in BCG with excess release of the STING agonist, c-di-AMP | Increased pro-inflammatory cytokine responses, greater myeloid cell reprogramming (M1 shift), enhanced epigenetic and metabolomic changes, and enhanced Teff infiltration | Improved protective efficacy vs bladder cancer (rat MNU model and mouse MB49 orthotopic model of NMIBC) |
| Singh et al., 2020 | |||
| Ref. 85bioRxiv | |||
| 2020.04.25.061531 | |||