Anti-Leukocyte Adhesion for the Mitigation of Potential Adverse Events caused by CD3-Specific Binding Domains

A kit comprising a compound as defined or identified in any one of the preceding claims, together with a CD3 binding domain.

A kit comprising a compound as defined or identified in any one of the preceding claims, together with a nucleic acid which encodes a chimeric antigen receptor (CAR).

A pharmaceutical composition comprising a compound as defined or identified in any one of the preceding claims, together with a CD3 binding domain.

A CD3 binding domain for use in a method of re-directing of T-cells against target cells in a patient, wherein said patient is subject to therapy comprising the compound as defined in any one of the preceding claims.

A nucleic acid which encodes a chimeric antigen receptor (CAR) for use in a method of re-directing of T-cells against target cells in a patient, wherein said patient is subject to therapy comprising the compound as defined in any one of the preceding claims.

Any one of the preceding claims, wherein said clinical adverse events comprise neurological adverse events.

Any one of the preceding claims, wherein said neurological adverse event is/are one or more of (i) cognitive disorder comprising disorientation/confusion and/or word finding problems/aphasia, (ii) seizure, (iii) cerebellar symptoms partly observed as an optional prodromal phase of (i) or (ii) comprising kinetic tremor, ataxia, dysarthria and handwriting problems.

Any one of the preceding claims, wherein said CD3 binding domain is a bispecific single chain antibody.

Any one of the preceding claims, wherein said bispecific single chain antibody is a CD19×CD3 bispecific single chain antibody.

Any one of the preceding claims, wherein said chimeric antigen receptor (CAR) comprises a CD19 binding domain.

Any one of the preceding claims, wherein said CD19×CD3 bispecific single chain antibody is MT103/AMG103.

Any one of the preceding claims, wherein said patient is characterized by a B/T-cell ratio of less than 1:5 or a B-cell number of less than about 50 B-cells per pi peripheral blood.

Any one of the preceding claims, wherein said compound is PPS, Minocyclin, or Natalizumab.

A method for prophylaxis, amelioration and/or treatment of clinical adverse events caused by therapy which comprises re-directing of T-cells against target cells in a patient, said method comprising administering a therapeutically effective amount of a compound defined in any one of the preceding claims.

Any one of the preceding claims, wherein said mammalian T-cells are re-directed mammalian T-cells.

Any one of the preceding claims, wherein said mammalian endothelial cells are isolated from large vessels or capillaries.

The compound of any one of the preceding claims, wherein said T-cell adhesion molecule is selected from integrins (such as alpha4-integrins;

• alphaL-beta2-integrins, alphaL-integrins, beta7-integrins), selectins (such as L-selectin), CD44, CD162 and/or Src-family kinases.

The compound of any one of the preceding claims, wherein said endothelial adhesion molecule is selected from selectins (such as E- or P-selectin);

• cell adhesion molecules CAMs (such as ICAM-1, MAdCAM, VCAM-1) and/or PAR-1.

Any one of the preceding claims, wherein said patient is a mammal, preferably a primate, most preferably a human being.