{"entity":{"id":"lymphoma-bio-lineage-antigen-cost","kind":"term","name":"What it costs to aim at a lineage antigen","aka":["Lineage antigen","On-target off-tumour toxicity","B-cell aplasia","Hypogammaglobulinaemia"],"tldr":"Almost every lymphoma drug that finds the cancer by a surface marker finds healthy cells carrying the same marker. The side effects are not accidents; they are the treatment working on the wrong cells, and they are predictable from the marker.","summary":"Nearly all the surface targets in lymphoma are what the corpus calls lineage antigens: normal proteins on a normal cell type, present on the cancer because the cancer came from that cell type. Only a few, such as CD30, are close to restricted to activated cells in an adult. This has consequences that can be read off the target before the first dose.\n\nCD20 and CD19 are on every normal B cell, so anti-CD20 and anti-CD19 treatments empty the B-cell compartment. What follows is low immunoglobulin, more bacterial and viral infection, a blunted response to vaccination, and, specifically, reactivation of hepatitis B, which is why surface antigen and core antibody are checked before the first dose of rituximab. After CAR-T the aplasia is deeper and longer, sometimes years, and immunoglobulin replacement is part of the plan rather than a rescue.\n\nCD52 is on B cells, T cells, monocytes and dendritic cells, so alemtuzumab produces the most profound lymphopenia of any antibody used in lymphoma, with CD4 counts that can stay low for a year, and with it cytomegalovirus reactivation, Pneumocystis pneumonia and fungal infection.\n\nCCR4 is on regulatory T cells as well as on the tumour, so mogamulizumab removes the cells that hold autoimmunity in check: rash is common, and giving it shortly before an allogeneic transplant has been associated with severe graft-versus-host disease.\n\nCD47 is on red cells, where its job is to tell a macrophage not to eat them, so blocking it causes anaemia by design; the dosing strategy that made the class usable is a low priming dose followed by higher maintenance doses.\n\nCD38 produces a laboratory problem rather than a clinical one: anti-CD38 antibodies bind CD38 on red cells and make the indirect antiglobulin test positive, masking real alloantibodies, so the transfusion laboratory must be warned before a crossmatch.\n\nCD3 is not on the tumour at all in B-cell disease: it is the handle a bispecific antibody uses to grip a T cell. Cytokine release syndrome and neurotoxicity are that mechanism working, which is why these drugs are given with step-up dosing.","asOf":"2026-09-30","links":[{"label":"Advani et al., N Engl J Med 2018: CD47 blockade with Hu5F9-G4 and rituximab in 22 patients with non-Hodgkin lymphoma","url":"https://doi.org/10.1056/NEJMoa1807315"},{"label":"Kim et al., Lancet Oncol 2018: MAVORIC, mogamulizumab against vorinostat in previously treated cutaneous T-cell lymphoma","url":"https://doi.org/10.1016/S1470-2045(18)30379-6"}],"tags":[],"related":[],"cancers":["non-hodgkin-lymphoma","dlbcl","cutaneous-t-cell-lymphoma","sezary-syndrome","peripheral-t-cell-lymphoma"],"sections":[],"technologies":["monoclonal-antibody","car-t","bispecific-antibody","t-cell-engager"],"targets":["cd20","cd19","cd52","ccr4","cd47","cd38","cd3","cd22","cd79b"],"drugs":[],"companies":[],"institutions":[],"pathways":["cd47-sirpa"],"terms":["lymphoma-bio-antigen-escape","lymphoma-tx-crs-icans","lymphoma-tx-immunoglobulin-replacement","lymphoma-tx-hepatitis-b-reactivation"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Cancer biology"},"route":"/terms/lymphoma-bio-lineage-antigen-cost/","neighbours":{"cancer":[{"id":"cutaneous-t-cell-lymphoma","kind":"cancer","name":"Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome)","route":"/cancers/cutaneous-t-cell-lymphoma/"},{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"angioimmunoblastic-t-cell-lymphoma","kind":"cancer","name":"Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma)","route":"/cancers/angioimmunoblastic-t-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"peripheral-t-cell-lymphoma","kind":"cancer","name":"Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma)","route":"/cancers/peripheral-t-cell-lymphoma/"},{"id":"sezary-syndrome","kind":"cancer","name":"Sezary syndrome","route":"/cancers/sezary-syndrome/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"},{"id":"car-t","kind":"technology","name":"CAR-T cell therapy","route":"/technologies/car-t/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"target":[{"id":"ccr4","kind":"target","name":"CCR4","route":"/targets/ccr4/"},{"id":"cd19","kind":"target","name":"CD19","route":"/targets/cd19/"},{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"},{"id":"cd22","kind":"target","name":"CD22","route":"/targets/cd22/"},{"id":"cd3","kind":"target","name":"CD3","route":"/targets/cd3/"},{"id":"cd38","kind":"target","name":"CD38","route":"/targets/cd38/"},{"id":"cd47","kind":"target","name":"CD47","route":"/targets/cd47/"},{"id":"cd52","kind":"target","name":"CD52","route":"/targets/cd52/"},{"id":"cd79b","kind":"target","name":"CD79b","route":"/targets/cd79b/"}],"pathway":[{"id":"cd47-sirpa","kind":"pathway","name":"CD47 / SIRPα (the 'don't eat me' signal)","route":"/pathways/cd47-sirpa/"}],"term":[{"id":"lymphoma-bio-antigen-escape","kind":"term","name":"Antigen escape: how a lymphoma loses the thing the drug was aimed at","route":"/terms/lymphoma-bio-antigen-escape/"},{"id":"lymphoma-tx-crs-icans","kind":"term","name":"Cytokine release syndrome and ICANS: grading and management","route":"/terms/lymphoma-tx-crs-icans/"},{"id":"lymphoma-tx-hepatitis-b-reactivation","kind":"term","name":"Hepatitis B reactivation before rituximab and other anti-CD20 antibodies","route":"/terms/lymphoma-tx-hepatitis-b-reactivation/"},{"id":"lymphoma-tx-immunoglobulin-replacement","kind":"term","name":"Immunoglobulin replacement after CAR-T, bispecifics and long anti-CD20 treatment","route":"/terms/lymphoma-tx-immunoglobulin-replacement/"}],"drug":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}],"biomarker":[{"id":"cd19-expression","kind":"biomarker","name":"CD19 expression (CD19-positive)","route":"/biomarkers/cd19-expression/"},{"id":"cd20-expression","kind":"biomarker","name":"CD20 expression (CD20-positive)","route":"/biomarkers/cd20-expression/"},{"id":"cd30-expression","kind":"biomarker","name":"CD30 expression (CD30-positive)","route":"/biomarkers/cd30-expression/"}]}}