Characterisation of a new murine B cell lymphoma

Cobb, L. M.; Glennie, Martin J.; McBride, H M; Breckon, G.; Richardson, T. C.

doi:10.1038/bjc.1986.244

Cited by 13 publications

(4 citation statements)

References 18 publications

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“…To ensure that the therapeutic benefit of anti-CD20/CD27 therapy was not confined to the BCL 1 model, the combination was also tested in the A31 B cell lymphoma ( Cobb et al., 1986 ) ( Figure 2 B) and Eμ-TCL1, B-chronic lymphocytic leukemia ( Bichi et al., 2002 ) models ( Figures 2 C–2E). In both models, anti-CD20 alone provided a modest therapeutic benefit.…”

Section: Resultsmentioning

confidence: 99%

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Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment

et al. 2017

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SummaryMonoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T cell responses. Here, we examined the therapeutic potential of combining a direct tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs. Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple lymphoma models, including huCD27 transgenic mice using the anti-huCD27, varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing demonstrated that anti-CD27 stimulated CD8+ T and natural killer cells to release myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration and macrophage activation. This study demonstrates the therapeutic advantage of using an immunomodulatory mAb to regulate lymphoid cells, which then recruit and activate myeloid cells for enhanced killing of mAb-opsonized tumors.

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Section: Resultsmentioning

confidence: 99%

“…BCL 1 ( Slavin and Strober, 1978 ) and A31 ( Cobb et al., 1986 ) B-cell lymphoma lines originated from female mice and were maintained by passage in BALB/c mice or CBA/H mice, respectively. The age of the source mice are not known.…”

Section: Methodsmentioning

confidence: 99%

Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment

et al. 2017

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“…Ten-to 12-wkold female BALB/c and CBA/H mice were supplied by Harlan UK (Blackthorn, Oxon, U.K.) and maintained in local animal facilities. BCL 1 (37) and A31 (38) mouse B lymphoma models and the 5T-33 myeloma (gift from Dr. N. Savelyeva) were maintained by in vivo passage in BALB/C, CBA, and C57BL/6 KA mice, respectively. Animal experiments were cleared through the local ethical committee and performed under Home Office licenses PPL30/2450 and 30/2451.…”

Section: Animals and Cellsmentioning

confidence: 99%

Immunotherapy Targeting Inhibitory Fcγ Receptor IIB (CD32b) in the Mouse Is Limited by Monoclonal Antibody Consumption and Receptor Internalization

Williams

Tutt²,

Beers

et al. 2013

The Journal of Immunology

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Genetic deficiency of the inhibitory Fc receptor, FcγRIIB (CD32b), has been shown to augment the activity of activatory FcγR and promote mAb immunotherapy. To investigate whether mAbs capable of blocking FcγRIIB have similar capacity, we recently generated a panel of specific anti-mouse FcγRIIB mAbs that do not cross-react with other FcRs, allowing us to study the potential of FcγRIIB as a therapeutic target. Previous work revealed a number of these mAbs capable of eliciting programmed cell death of targets, and in the present study we demonstrated their ability to promote target cell phagocytosis. However, in a variety of murine tumor models, anti-FcγRIIB mAbs demonstrated limited therapeutic activity despite optimized treatment regimens. Unexpectedly, we observed that the anti-FcγRIIB mAbs are rapidly and extensively consumed in vivo, both by the tumor and host cells, including B cells, leading to a precipitous loss from the circulation. Closer analysis revealed that the anti-FcγRIIB mAbs become extensively internalized from the cell surface within 24 h in vivo, likely explaining their suboptimal efficacy. Subsequent studies revealed that anti-FcγRIIB mAb immunotherapy was effective when used against FcγRIIB+ tumors in FcγRIIB−/− recipients, indicating that consumption of the mAb by nontumor cells is the primary limitation of these reagents. Importantly, similar rates of internalization were not seen on human target cells, at least in vitro. These studies further highlight the need to determine the propensity of mAb therapeutics to internalize target receptors and also identify potential key differences between human and mouse cells in this respect.

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“…The A31 14 and BCL 1 15 B-lymphoma lines were maintained by in vivo passage in BALB/c and CBA/H mice, respectively. The BCL 1 variant of the BCL 1 tumor can be maintained both in vivo and in liquid culture.…”

Section: Micementioning

confidence: 99%

Anti-CD40 monoclonal antibody therapy in combination with irradiation results in a CD8 T-cell–dependent immunity to B-cell lymphoma

Honeychurch

Glennie

Johnson

et al. 2003

Blood

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The mechanisms of interaction between anti-CD40 monoclonal antibody (mAb) therapy and external beam irradiation were investigated in 2 syngeneic B-cell lymphoma models. We have established doses of anti-CD40 mAb and irradiation which, although ineffective when given singly, were capable of providing longterm protection when used in combination. Furthermore, such treatment was not only critically dependent on the dose of mAb and irradiation but also on tumor load, with greater efficacy only occurring at higher tumor burden. Using blocking antibody, the potency of treatment was shown to be totally dependent on CD8 ؉ T cells, with protective levels of CD8 ؉ cells occurring only in mice receiving the combination of anti-CD40 and irradiation. Interestingly, the ratio of T cells (CD8 ؉ ) to tumor cells in mice receiving combination treatment was between 10 and 15 times that seen in animals given anti-CD40 or irradiation alone. In vivo tracking experiments revealed a 2-phase decrease in tumor burden, the first resulting directly from the external irradiation and the second, occurring 5 days later, concomitant with the rise in tumor-specific CD8 ؉ cells. We suggest that the external irradiation induced an initial kill of lymphoma cells, probably by apoptosis, which releases tumor antigens and slows the progression of the malignancy to allow generation of a curative cytotoxic T lymphocyte (CTL) response promoted by the anti-CD40 mAb. Combining irradiation with immunomodulatory mAb as described here appears to provide a powerful new approach to the management of

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Characterisation of a new murine B cell lymphoma

Cited by 13 publications

References 18 publications

Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment

Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment

Immunotherapy Targeting Inhibitory Fcγ Receptor IIB (CD32b) in the Mouse Is Limited by Monoclonal Antibody Consumption and Receptor Internalization

Anti-CD40 monoclonal antibody therapy in combination with irradiation results in a CD8 T-cell–dependent immunity to B-cell lymphoma

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