Journal: Clinical & Translational Immunology

Article Title: Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8 + T cells

doi: 10.1002/cti2.70014

Figure Lengend Snippet: CD47 × PD‐L1 BisAb therapy reduces tumor burden and induces CD8 + T cell expansion. Mice were orthotopically inoculated with AT3‐OVA cells and treated with 40 mg kg −1 of isotype or CD47 × PD‐L1 BisAb i.p from Day 10 post inoculation every 3–4 days for a total of five injections before being assessed on Day 28. (a) Experimental schematic. (b) Tumor volume over time. (c) Tumor volume at experimental endpoint (Day 28). Enumeration of macrophages, monocytes and neutrophils in the (d) spleen and (e) tumor. Enumeration of polyclonal CD44 hi CD4 + T cells, CD44 hi CD8 + T cells and SIINFEKL + CD8 + T cells in the (f) spleen and (g) tumor. Enumeration of cells in the tumor are expressed per mm 3 . The combined data of two independent experiments with a total of 9 or 10 mice per group is shown. ns, P > 0.05, * P ≤ 0.05, ** P ≤ 0.01, *** P ≤ 0.001, **** P ≤ 0.0001, Mann–Whitney U ‐test. Bars represent mean ± SEM, symbols represent individual mice.

Article Snippet: Mice used in this study weighed an average of 20 g. Mice were treated with 40 mg kg −1 mouse CD47 × PD‐L1 bispecific antibody (Pfizer Inc. ); 40 mg kg −1 mouse IgG2a isotype control (Leica Biosystems, Wetzlar, Germany) or 10 mg kg −1 mouse anti‐PD‐L1 (Clone 10F.6G2, Bio X Cell, Lebanon, USA) via intraperitoneal injection on days 10, 13, 16, 20 and 24 after tumor inoculation.

Techniques: MANN-WHITNEY

Journal: Clinical & Translational Immunology

Article Title: Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8 + T cells

doi: 10.1002/cti2.70014

Figure Lengend Snippet: CD47 × PD‐L1 BisAb therapy enhances tumor‐resident CD8 + TIL formation and function. (a–j) AT3‐OVA‐bearing mice were treated with isotype or BisAb before being assessed on Day 28 post inoculation. (a) Representative contour plots and (b) frequency of CD69 and CD62L expression by CD44 hi CD8 + T cells in the spleen. Shaded boxes in (a) represent the frequency of CD69 + CD62L − T cells. (c) Representative contour plots and (d) frequency of T EM (CD127 + CD62L − ), T CM (CD127 + CD62L + ) and LLEC (CD127 − CD62L − ) CD44 hi CD8 + T cells in the spleen. (e) Representative contour plots and (f) frequency of CD69 and CD62L expression by SIINFEKL + CD8 + T cells in the tumor. Shaded boxes in (e) represent the frequency of CD69 + CD62L − T cells. (g) Representative contour plots and (h) frequency of CD69 and CD103 expression by SIINFEKL + CD8 + T cells in the tumor. Enumeration of (i) CD44 hi CD8 + and (j) SIINFEKL + CD69 − , CD69 + CD103 − and CD69 + CD103 + TIL. (k, l) Intratumoral CD8 + T cells were stimulated with PMA/Ionomycin Day 18 post‐inoculation. (k) Representative contour plots of IFNγ expression by CD69 + CD103 + TIL. (l) Frequency of IFNγ expression by CD69 − T CIRC , CD69 + CD103 − and CD69 + CD103 + TIL. Enumeration of cells in the tumor are expressed per mm 3 . The combined data of two independent experiments with a total of 9 or 10 mice (b, d, f, g, h) and 4–6 mice (j) per group is shown. ns, P > 0.05, ** P ≤ 0.01, *** P ≤ 0.001, **** P ≤ 0.0001, Mann–Whitney U ‐test. Bars represent mean ± SEM, symbols represent individual mice.

Article Snippet: Mice used in this study weighed an average of 20 g. Mice were treated with 40 mg kg −1 mouse CD47 × PD‐L1 bispecific antibody (Pfizer Inc. ); 40 mg kg −1 mouse IgG2a isotype control (Leica Biosystems, Wetzlar, Germany) or 10 mg kg −1 mouse anti‐PD‐L1 (Clone 10F.6G2, Bio X Cell, Lebanon, USA) via intraperitoneal injection on days 10, 13, 16, 20 and 24 after tumor inoculation.

Techniques: Expressing, MANN-WHITNEY

Journal: Clinical & Translational Immunology

Article Title: Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8 + T cells

doi: 10.1002/cti2.70014

Figure Lengend Snippet: CD47 × PD‐L1 BisAb‐mediated tumor control is dependent on CD8 + T cells. Mice were inoculated with AT3‐OVA prior to administration of 10 mg kg −1 of anti‐CD8α every 2–3 days from Day 8 post inoculation. On Day 10 post inoculation, mice were treated with 40 mg kg −1 of isotype or BisAb i.p and assessed at Day 28. (a) Experimental schematic. (b) Enumeration of CD44 hi CD8 + T cells in the spleen and tumor. (c) Tumor volume over time. (d) Tumor volume at experimental endpoint (Day 28). Enumeration of cells in the tumor are expressed per mm 3 . The combined data of two independent experiments with a total of 7 or 8 mice per group is shown. P > 0.05, * P ≤ 0.05, ** P ≤ 0.01, *** P ≤ 0.001, **** P ≤ 0.0001, one‐way ANOVA with a Kruskal–Wallis post‐test. Bars represent mean ± SEM, symbols represent individual mice.

Article Snippet: Mice used in this study weighed an average of 20 g. Mice were treated with 40 mg kg −1 mouse CD47 × PD‐L1 bispecific antibody (Pfizer Inc. ); 40 mg kg −1 mouse IgG2a isotype control (Leica Biosystems, Wetzlar, Germany) or 10 mg kg −1 mouse anti‐PD‐L1 (Clone 10F.6G2, Bio X Cell, Lebanon, USA) via intraperitoneal injection on days 10, 13, 16, 20 and 24 after tumor inoculation.

Techniques: Control

Journal: Clinical & Translational Immunology

Article Title: Dual CD47 and PD‐L1 blockade elicits anti‐tumor immunity by intratumoral CD8 + T cells

doi: 10.1002/cti2.70014

Figure Lengend Snippet: CD47 × PD‐L1 BisAb treatment is superior to anti‐PD‐L1 monotherapy. AT3‐OVA bearing mice were treated with 40 mg kg −1 of isotype or BisAb, or 10 mg kg −1 of anti‐PD‐L1 i.p every 3–4 days from Day 10 post inoculation before being assessed on Day 28. (a) Experimental schematic. (b) Tumor volume over time. (c) Tumor volume at experimental endpoint (Day 28). (d) Tumor growth inhibition expressed as a percentage of endpoint tumor volume measured for the isotype control. Each point represents one independent experiment, where average tumor volume per group was employed to calculate differences between groups. (e) Fold‐change increase in enumerated CD44 hi and SIINFEKL + CD8 + T cells in the tumor from isotype control. (f) Enumeration of IFNγ + CD8 + T cells in the tumor and spleen upon PMA/Ionomycin stimulation. Enumeration of cells in the tumor are expressed per mm 3 . The combined data of three independent experiments with a total of 10–12 mice per group is shown. ns, P > 0.05, * P ≤ 0.05, ** P ≤ 0.01, *** P ≤ 0.001, one‐way ANOVA. Bars represent mean ± SEM, symbols represent individual mice.

Article Snippet: Mice used in this study weighed an average of 20 g. Mice were treated with 40 mg kg −1 mouse CD47 × PD‐L1 bispecific antibody (Pfizer Inc. ); 40 mg kg −1 mouse IgG2a isotype control (Leica Biosystems, Wetzlar, Germany) or 10 mg kg −1 mouse anti‐PD‐L1 (Clone 10F.6G2, Bio X Cell, Lebanon, USA) via intraperitoneal injection on days 10, 13, 16, 20 and 24 after tumor inoculation.

Techniques: Inhibition, Control

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: List of “don’t eat me signaling pathways.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques: Blocking Assay, Activation Assay, Expressing

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Depiction of CD47/SIRPα signaling pathway. CD47 is overexpressed on the surface of cancer cells, acting as a “don’t eat me” signal. SIRPα is a receptor on the surface of macrophages and dendritic cells. When CD47 binds to SIRPα, it sends an inhibitory signal to the myeloid cells. This interaction inhibits the phagocytic activity of the myeloid cells, preventing them from engulfing and destroying cancer cells, thus allowing the cancer cells to evade the immune system.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques: Activity Assay

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Depiction of CD47 and SIRPα structures.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Depiction of mechanism of actions targeting CD47/SIRPα axis. The anti-SIRPα mAbs bind to SIRPα and SIRPα-Fc fusion proteins bind to FcγR on macrophages (left panel), while anti-CD47 mAbs SIRPα-Fc fusion proteins bind to CD47 on tumor cells (right panel).

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Categories for CD47 antagonist products.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: CD47 antagonists currently entering clinical trials for treatment of ovarian cancers.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: CD47 related ongoing clinical trials in breast cancers.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: CD47 antagonists currently entering clinical trials for treatment of lymphomas.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: CD47 agents currently entering clinical trials for treatment of hematological malignancies except lymphoma.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques: Transplantation Assay

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Targeting CD47 related clinical trials have been terminated.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques: Binding Assay, Mutagenesis

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Prerequisites for macropage activation. In a normal situation, CD47 binds to SIRPα, acting as the “don’t eat me” signal, and no “eat me” signal is present. Therefore, there is no or poor macrophage activation (A) . When only CD47 is blocked, the “don’t eat me” signal is inhibited. However, no “eat me” signal is activated, resulting in only limited macrophage activation (B) . When the CD47 “don’t eat me” signal is present, and only the Fc-receptor “eat me” signal is activated, there is still only limited macrophage activation (C) . When both CD47 is blocked and the Fc-receptor “eat me” signal is activated, full macrophage activation occurs (D) .

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques: Activation Assay

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Potential tactics for future exploration of CD47-targeted therapeutic agents.

Article Snippet: NCT05189093 , HX-009 (HX-009–5) , Phase II , Recruiting , 99 , HanX Biopharmaceuticals Inc , CD47 antagonist , anti-CD47/PD-L1 BsAb , Lymphoma.

Techniques: Modification, Plasmid Preparation, Blocking Assay, Activation Assay

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: List of “don’t eat me signaling pathways.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques: Blocking Assay, Activation Assay, Expressing

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Depiction of CD47/SIRPα signaling pathway. CD47 is overexpressed on the surface of cancer cells, acting as a “don’t eat me” signal. SIRPα is a receptor on the surface of macrophages and dendritic cells. When CD47 binds to SIRPα, it sends an inhibitory signal to the myeloid cells. This interaction inhibits the phagocytic activity of the myeloid cells, preventing them from engulfing and destroying cancer cells, thus allowing the cancer cells to evade the immune system.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques: Activity Assay

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Depiction of CD47 and SIRPα structures.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Depiction of mechanism of actions targeting CD47/SIRPα axis. The anti-SIRPα mAbs bind to SIRPα and SIRPα-Fc fusion proteins bind to FcγR on macrophages (left panel), while anti-CD47 mAbs SIRPα-Fc fusion proteins bind to CD47 on tumor cells (right panel).

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Categories for CD47 antagonist products.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: CD47 antagonists currently entering clinical trials for treatment of ovarian cancers.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: CD47 related ongoing clinical trials in breast cancers.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: CD47 antagonists currently entering clinical trials for treatment of lymphomas.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques:

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: CD47 agents currently entering clinical trials for treatment of hematological malignancies except lymphoma.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques: Transplantation Assay

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Targeting CD47 related clinical trials have been terminated.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques: Binding Assay, Mutagenesis

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Prerequisites for macropage activation. In a normal situation, CD47 binds to SIRPα, acting as the “don’t eat me” signal, and no “eat me” signal is present. Therefore, there is no or poor macrophage activation (A) . When only CD47 is blocked, the “don’t eat me” signal is inhibited. However, no “eat me” signal is activated, resulting in only limited macrophage activation (B) . When the CD47 “don’t eat me” signal is present, and only the Fc-receptor “eat me” signal is activated, there is still only limited macrophage activation (C) . When both CD47 is blocked and the Fc-receptor “eat me” signal is activated, full macrophage activation occurs (D) .

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques: Activation Assay

Journal: Frontiers in Oncology

Article Title: Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives

doi: 10.3389/fonc.2024.1378647

Figure Lengend Snippet: Potential tactics for future exploration of CD47-targeted therapeutic agents.

Article Snippet: NCT04881045 , PF-07257876 , Phase I , Active_not_recruiting , 28 , Pfizer , CD47 antagonist , anti-CD47/PD-L1 BsAb , OC/NSCLC.

Techniques: Modification, Plasmid Preparation, Blocking Assay, Activation Assay