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. 2023 May 9;7(9):1666-1670.
doi: 10.1182/bloodadvances.2022008303.

Preclinical studies targeting CD74 with STRO-001 antibody-drug conjugate in acute leukemia

Quy Le  1 , Thao Tang  1 , Amanda Leonti  1 , Sommer Castro  1 , Cyd Nourigat McKay  1 , LaKeisha Perkins  1 , Laura Pardo  2 , Danielle Kirkey  1 , Tiffany Hylkema  1 , Lindsey Call  1 , Makia Manselle  1 , Cristina Abrahams  3 , Kristin Bedard  3 , Arturo Molina  3 , Lisa Eidenshinck Brodersen  2 , Michael R Loken  2 , Katherine Tarlock  1   4 , Soheil Meshinchi  1   5   4 , Keith R Loeb  1   6
Affiliations

Preclinical studies targeting CD74 with STRO-001 antibody-drug conjugate in acute leukemia

Quy Le et al. Blood Adv. .
No abstract available

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Conflict of interest statement

Conflict-of-interest disclosure: L. Pardo, L.E.B. and M.R.L. are employees of Hematologics Inc.; and M.R.L. has equity ownership in Hematologics Inc. C.A., K.B., and A.M. are employees of Sutro Biopharma. All other authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
STRO-001 therapy demonstrates preclinical efficacy against CD74 expressing NOMO-1 AML cell line and primary AML cells. (A) Flow cytometric analysis of CD74 cell surface expression on K562 and NOMO-1 cell lines. (B) In vitro cytotoxicity of STRO-001 against K562 and NOMO-1 cells. Cells were treated with increasing doses of STRO-001 alone (blue) or excess of naked antibody SP7219 (1 uM, red). After 3 days of continuous exposure, viability was assessed by Cell Titer-Glo assay. Data are normalized to untreated controls. Error bars denote standard deviation from 2 technical replicates at each dose. Experiments were repeated at least twice (supplemental Figure 5). (C) Top, experimental schema evaluating STRO-001 in vivo efficacy in NOMO-1 xenograft model. Bottom, leukemia burden measured by bioluminescence (IVIS) imaging in NOMO-1 xenograft mice untreated (left) or treated with STRO-001 at 3 mg/kg weekly for 3 weeks (right). Shown are representative timepoints. N = 5 mice per group. X denotes death. (D) Kaplan-Meier survival curves of NOMO-1 xenografts untreated or treated with STRO-001. N = 5 per group. Statistical differences in survival were evaluated using Log-rank Mantel-Cox. (E) Flow cytometric analysis of CD74- (AML-4) and CD74+ AML patient specimens (AML-5-7). (F) In vitro cytotoxicity of STRO-001 primary AML specimens. Cells were treated as described above. Error bars denote standard deviation from 3 technical replicates at each dose. (G) Experimental design to assess in vivo activity of STRO-001 against a PDX model transplanted with a primary AML sample, AML-7. Peripheral blood was obtained every other week following the last dose of STRO-001, bone marrow aspirate was obtained 4 and 13 weeks after transplant. (H) Percent AML cells in the bone marrow at indicated weeks following leukemia injection determined by flow cytometry. (I) Kaplan-Meier survival curves of PDX mice untreated (n = 3) or treated with STRO-001 (n = 3). Statistical differences in survival were evaluated using Log-rank Mantel-Cox.
Figure 1.
Figure 1.
STRO-001 therapy demonstrates preclinical efficacy against CD74 expressing NOMO-1 AML cell line and primary AML cells. (A) Flow cytometric analysis of CD74 cell surface expression on K562 and NOMO-1 cell lines. (B) In vitro cytotoxicity of STRO-001 against K562 and NOMO-1 cells. Cells were treated with increasing doses of STRO-001 alone (blue) or excess of naked antibody SP7219 (1 uM, red). After 3 days of continuous exposure, viability was assessed by Cell Titer-Glo assay. Data are normalized to untreated controls. Error bars denote standard deviation from 2 technical replicates at each dose. Experiments were repeated at least twice (supplemental Figure 5). (C) Top, experimental schema evaluating STRO-001 in vivo efficacy in NOMO-1 xenograft model. Bottom, leukemia burden measured by bioluminescence (IVIS) imaging in NOMO-1 xenograft mice untreated (left) or treated with STRO-001 at 3 mg/kg weekly for 3 weeks (right). Shown are representative timepoints. N = 5 mice per group. X denotes death. (D) Kaplan-Meier survival curves of NOMO-1 xenografts untreated or treated with STRO-001. N = 5 per group. Statistical differences in survival were evaluated using Log-rank Mantel-Cox. (E) Flow cytometric analysis of CD74- (AML-4) and CD74+ AML patient specimens (AML-5-7). (F) In vitro cytotoxicity of STRO-001 primary AML specimens. Cells were treated as described above. Error bars denote standard deviation from 3 technical replicates at each dose. (G) Experimental design to assess in vivo activity of STRO-001 against a PDX model transplanted with a primary AML sample, AML-7. Peripheral blood was obtained every other week following the last dose of STRO-001, bone marrow aspirate was obtained 4 and 13 weeks after transplant. (H) Percent AML cells in the bone marrow at indicated weeks following leukemia injection determined by flow cytometry. (I) Kaplan-Meier survival curves of PDX mice untreated (n = 3) or treated with STRO-001 (n = 3). Statistical differences in survival were evaluated using Log-rank Mantel-Cox.
Figure 2.
Figure 2.
STRO-001 therapy demonstrates preclinical efficacy against CD74-positive B-ALL cell lines and primary B-ALL. (A) Flow cytometric analysis of CD74 cell surface expression on REH and RS4;11 B-ALL cell lines. (B) In vitro cytotoxicity of STRO-001 against REH and RS4;11 cells. Experiments were repeated twice (supplemental Figure 4). Data are normalized to untreated controls. Error bars denote standard deviation from 2 or 3 technical replicates at each dose. (C) Top, experimental schema evaluating STRO-001 in vivo efficacy in REH and RS4;11 xenograft models. Bottom, representative images of leukemia burden detected by IVIS imaging in REH and RS4;11 xenograft mice untreated or treated with STRO-001 at 3 mg/kg weekly for 3 weeks. N = 5 mice per group. X indicates death. (D) Quantification of radiance shown in C. N = 5 mice per group. (E) Kaplan-Meier survival curves of REH and RS4;11 xenograft mice untreated or treated with STRO-001. N = 5 per group. Statistical differences in survival were assessed by Log-rank Mantel-Cox test. (F) Flow cytometric analysis of CD74 expression in patient specimen B-ALL-3. (G) Percent B-ALL-3 cells (huCD19+) in the bone marrow at indicated weeks following leukemia injection (H) Kaplan-Meier survival curves of PDX B-ALL-3 mice untreated or treated with STRO-001. Data are presented as mean +/− SEM. Statistical differences were determined by unpaired, 2-tailed Student t test. Details of the B-ALL-3 PDX studies (8.5e6 cells/mouse; n = 4 for untreated group, n = 7 for STRO-001-treated group).
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References

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