Table 2 Antibodies in development for pre-HCT bone marrow conditioning

Vedolizumab

α4β7 integrin MAb

Phase 1b

AML, ALL, MDS

24: 3 Low Dose (LD),

21 High Dose (HD)

TTE: LD = 22, HD = 14

aGvHD 2–4: LD = 0%, HD = 19%

1 yr OS: LD = 66.6%, HD = 84.7%

[40]

Vedolizumab

α4β7 integrin MAb

Phase 3

Haem malignancy, myeloproliferative disorder

343

Ongoing

[41]

JSP191

CD117 MAb

Phase 1/2

AML, MDS, SCID, FA

40, 40, 12 (Estimated)

Ongoing

[46,47,48,49]

FSI-174 + Magrolimab

CD117MAb + CD47 MAb

Rhesus Macaques

None

Undisclosed

Significant depletion of HSCs

[43]

ACK-2 + anti-CD47 MAb

Anti-Mouse

CD117 Mab

Mice

None

–

 > 99% HSC depletion

[50]

Six-antibody

cocktail

Anti-CD4, CD8, CD40L, CD47, CD117, CD122

Mice

None

5

52% Donor granulocyte chimerism at 8 weeks

[51]

CD45-SAP

CD45 ADC

Mice

None

5

99% Host HSC depletion

4mo 90% HSC donor chimerism

Reduced toxicity versus TBI

[53]

CD45-SAP

CD45 ADC

Mice

SCID

–

91.7–95/2% Host HSC depletion

32.04–100% Donor HSC chimerism

[55]

CD117-SAP

CD117 ADC

Mice

None

3–5

 > 99% Host HSC depletion

98% Donor myeloid chimerism

 > 99% BM HSC donor chimerism

[56]

CD117 Saporin

 + anti-CD4, CD8, CD40L MAbs

CD117 ADC

Mice

None

15

High and sustained donor chimerism in 14/15 mice

Tolerance to skin allograft

[57]

CD117-SAP

CD117 ADC

Mice

Haemophilia A

6

Robust depletion of HSCs

90.6% Donor myeloid chimerism at 4 weeks

[58]

MGTA-117

CD117 ADC

Mice

AML

3

 > 95% Host HSPC depletion

Dual benefit as conditioning and anti-tumour treatment

[61]

DCR-2-PBD

CD300f ADC

Mice

AML

5

97% Reduction in total CD34 + cells

Selective depletion of myeloid cells

[72]

CD45-SAP or

CD117-SAP

45 and 117 ADCs

Mice

FA

16

Significant depletion of HSCs

Improved engraftment versus cytarabine-conditioned group

[73]

CD45-SAP + CD117-SAP + Baricitinib

45 and 117 ADCs

Mice

None

35

Significant depletion of HSCs

99% Donor myeloid chimerism

[74]

Iomab-B

CD45 RlAb

Phase 3

AML

153

Trial ongoing: preliminary results:

99% Depletion of circulating blasts

91% of patients > 95% donor chimerism

[79,80,81,82]

90Y-BC8

CD45 RlAb

Phase 1

AML, CML, MDS, ALL, RA

15

87% complete remission

All engrafted by day 28

2 yr OS 46%

[83, 84]

90Y-BC8

CD45 RlAb

Phase 1

Plasma Cell Myeloma

15

0% TRM

100% Donor chimerism of CD3 and CD33 cells

5 yr OS/PFS = 71%/41%

[85]

90Y-BC8

CD45 RlAb

Phase 1

B-NHL, T-NHL, HL

21

0% Day 100 NRM

Median day 13 neutrophil and platelet engraftment

5 yr OS/PFS = 68%/37%

[86]

131I-BC8

CD45 RlAb

Phase 2

AML, MDS

15

Completed, no results

[87]

211A-BC8-B10

CD45 RlAb

Phase

Non-Malignant Neoplasms

40 (Estimated)

Recruiting

[88]

211A-BC8-B10

CD45 RlAb

Phase 1/2

AML, ALL, MDS, AL, CML

50 (Estimated)

Recruiting

[89]

90Y-Daclizumab

CD25 RlAb

Phase 1/2

HL

4

100% CR ongoing 4.5–7 yr

[102]

90Y-Anti-CD25

CD25 RlAb

Phase 2

HL

33 (Estimated)

Recruiting

[103]

90Y-Basiliximab

CD25 RlAb

Phase 1

NHL

20 (Estimated)

Ongoing

[104]

90Y-Anti-CD66

CD66 RlAb

Phase 2

AML, ALL, MDS, immuno-deficiency, anaemia

30

93% Stable engraftment

43% Malignant disease relapse, 6% non-malignant relapse

37% aGvHD, 17% cGvHD

94% 2 yr OS non-malignant group

69% 2 yr OS malignant group

[108]

90Y-Anti-CD66

CD66 RlAb

Phase 1

Paediatric leukaemia

9

Completed, no results

[109]

90Y-Anti-CD66

CD66 RlAb

Phase 1/2

Leukaemia, myeloma, lymphoma

62

Completed, no results

[110]

90Y-Anti-CD66

CD66 RlAb

Phase 2

Paediatric leukaemia

25 (Estimated)

Active, not yet recruiting

[111]

Anti-CD7 CAR with CXCR4 receptor

Anti CD7-CAR-T

Mice

None

5

27% LT-HSC donor chimerism

20–30% PB granulocyte, B and T cell donor chimerism

[113]

Anti-CD117

CAR-T*

Anti-CD7 CAR-T

Mice

None

10

98% CD117 + cell elimination

Reduction in bone marrow cellularity

[114]

Anti-CD123-

CAR-T*

Anti-CD123-CAR-T

Mice

AML

31

Eradication of normal haematopoiesis in CD34 + cell transplanted mice

[115]

Anti-CD123-

CAR-T*

Anti-CD123-CAR-T

Mice

None

-

Reduced CD34 + cell clonogenic capacity

Impaired self-haematopoietic system reconstitution

[116]

CD34-CD3

BiTE*

CD34-CD3 BiTE

Mice

None

5

Reduced BM and splenic tumour burden, HSC depletion

[118]

FLT3-CD3 BiTe

FLT3-CD3 BiTe

Mice

AML

5

Increased PD-1 expression on T cells

Decreased PB leukaemic burden

Modest survival advantage compared to PD-1 treatment

[120]